The embryonic structure that gives rise to CNS structures is the neural tube.
When the neural tube is formed it differentiates into the brain rostrally and spinal cord caudally.
Anteriorly begins to expand and forms the three primary brain vesicles.
Primary brain vesicles
Secondary brain vesicles – by 5th week
Sprouts “ears” – cerebral hemispheres
Also gives rise to lateral ventricles and superior part of 3rd ventricle
Thalamus, hypothalamus, epithalamus
Most of 3rd ventricle
Brain stem: midbrain
Brain stem: pons
Brain stem: medulla oblongata
Flexures develop due to restriction of skull
Midbrain and cervical flexures bend forebrain toward brain stem
Cerebral hemispheres grow posteriorly and laterally in a horseshoe shape, creases and folds to form convolutions
Increases surface area accomodates around one trillion neurons
Regions and Organization of the Brain
Diencephalon (sometimes grouped with either brain stem or cerebrum)
Organization of CNS
Spinal cord – central cavity surrounded by gray matter surrounded by white matter
Brain – central cavity surrounded by gray matter surrounded by white matter with some exceptions: Outer cortex of gray matter in cerebrum and cerebellum, scattered gray matter (nuclei) within white matter or brain stem
Ventricles of the Brain
Spaces within the brain
Connected to each other and the spinal cord’s central canal
Lined with ependymal cells
Lateral ventricles (1st and 2nd ventricles)
One in each cerebral hemisphere
Close anteriorly, separated by septum pellucidum (thin membranous structure
Connected to 3rd ventricel by interventricular foramen (Foramen of Monro)
Located in diencephalon
Cerebral aqueduct connects to 4th ventricle
Dorsal to pons and superior to medulla
Continuous with central canal of spinal cord inferiorly
Connected to subarachnoid space by 2 lateral apertures and median aperature
Gyri (Jeer-ee) – folds
Sulci (sul-kee ) – grooves
Fissure – deep groove
Longitudinal fissure separates hemispheres
Transverse fissure separates cerebrum from cerebellum
Central sulcus – separates frontal lobe from parietal lobe
Precentral gyrus – anterior
Postcentral gyrus - posterior
Parieto-occipital sulcus separates parietal lobe and occipital lobe
Lateral sulcus separates temporal lobe from parietal and frontal lobes
Insula – 5th lobe, buried in lateral sulcus
Seat of consciousness
Gray matter – cell bodies, dendrites, unmyelinated axons, glia, blood vessels; no fiber tracts
52 different areas mapped by variations in thickness and structure of neurons
Functional aspects: domains
Specific motor and sensory functions localized in domains
Accommodates the Regional Specialization Theory (Structurally distinct areas have specific functions)
Higher mental functions (memory and language) have overlapping domains, or at least receive input from and send output to different domains
Accommodates the Aggregate Field View (Cortex acts as a whole to carry out mental functions)
Three functional areas: motor, sensory, and association
Lateralization of function
All functional areas interact with other areas in some way
Primary motor cortex (somatic motor cortex)
Located in precentral gyrus of frontal lobe of each hemisphere
Directs conscious movement of SkM
Axons of pyramidal cells in precentral gyrus run down spinal cord; form voluntary motor tracts called pyramidal tracts or corticospinal tracts
All other descending motor tracts come from brain stem nuclei and have 2 or more neurons in a chain
Somatotopy and the motor homunculus – localization of body structures to neurons that control them
Actually shown that neurons innervate more than one muscle (synergists)
Muscles receive input from more than one site on the cortex
Anterior to precentral gyrus
Controls practiced motor skills of a repetitive nature; coordinates movement of several muscle groups simultaneously
Anterior to the inferior region of the premotor cortex
Thought to be present in only one hemisphere – usually the left – concerned with motor speech; direction of muscles used to speak
Broca’s area and a corresponding area in the other hemisphere both are active just before speech and during the “planning” phase preceding other voluntary motor activities.
Frontal eye field
Anterior to premotor coretex and superior to Broca’s area
Controls voluntary eye movements
Primary somatosensory cortex
Receive input from general sensory receptors in skin and proprioceptors in SkM
Identify region being stimulated – spatial discrimination
Somatosensory association area
Posterior to the primary somatosensory cortex
Integrates and analyzes somatic sensory input
Lets you stick your hand in your pocket and know what you’re grabbing
Primary visual cortex
Located on posterior tip of occipital lobe and within calcarine sulcus on the medial aspect of the occipital lobe
Largest cortical sensory area
Receives input from retinas
Contralateral – right half of visual space from each eye sends input to the left visual cortex and vice versa
Visual association area
Surrounds primary visual area
Interprets visual stimuli, enables recognition
Damage to primary visual cortex = blindness; damage to visual association area = see it but don’t know what it is
Primary auditory cortex
superior margin of temporal lobe
input from cochlear receptors of inner ear
Auditory association area
Integrates; tells you what you heard
Sound memories stored here (what it is, not so much what it means)
Piriform lobe in medial aspect of temporal lobes
Part of rhinencephalon, now associated with emotion and memory (limbic system)
Insula, deep to temporal lobe
Visceral sensory area
Posterior to the gustatory cortex in the insula
Conscious perception of visceral sensations
Vestibular (equilibrium) cortex
Posterior part of insula
Conscious perception of balance
Multimodal Association Areas
Any cortical area that doesn’t have primary in its name (not primarily linked to one sensory or motor area)
Communicate with the motor cortex and other sensory association areas; analyze, recognize, act on input
Have multiple inputs and outputs independent of primary sensory and motor areas
Anterior Association Area (Prefrontal cortex)
Most complicated cortical region
Intellect, complex learning, personality
Abstract ideas, judgment, reasoning, persistence, planning concern for others, and conscience
Linked to limbic system, role in mood
Prefrontal lobotomy – treatment of severe mental illness (‘30s to ‘50s); reduced anxiety (and judgment, initiative, spurred abnormal personality changes, caused epilepsy, etc.)
Posterior Association Area (General interpretation area or gnostic area)
Input from all sensory association areas
Storage site for complex memories associated with sensation
Integrates input into understanding of situation, sends assessment to prefrontal cortex
Prefrontal cortex adds emotion and decides on response
Damage to this area results in inability to interpret situations (imbecility) Found in one hemisphere only (usually left)
Language areas – included in posterior association area
Occurs in posterior temporal lobe of one hemisphere (usually the left)
Speech area; once thought to be the only area responsible for understanding both written and spoken language
May be the phonics area; comprehension may occur in prefrontal areas
A newly discovered brain region, implicated in language.
Connects Broca's and Wernicke's areas via a region of the parietal lobe of the cortex, and may be important for the acquisition of language in childhood.
Apparently the last area in the brain to mature, the completion of its maturation coinciding with the development of reading and writing skills.
Affective language areas
Present in hemisphere opposite Broca’s and Wernicke’s areas
Affect – tone, both to impart and to interpret
Add emotional input to speech, interpret emotional content of speech
Limbic Association Area
Cingulate gyrus, parahippocampal gyrus, and the hippocampus
Provides emotional impact and helps establish memories
Lateralization of Cortical Functioning
Division of labor
Most functions performed by both hemispheres
Some dominance of tasks by one side or the other
The hemisphere that is dominant for language (also tends to have greater control over mathematical abilities and logic)
Left side in about 90% of people
Other side does visual-spatial skills, intuition, emotion, appreciation of art and music; poetic, creative
Usually left dominant people are right handed
Other 10% either reversed or “bilateral”
Typically left handed (although most lefties are left dominant, just right motor dominant)
Ambidexterity sometimes, sometimes cerebral confusion; dyslexia?
Communication and control over each other
Rational brain keeps emotional brain from running amuck, emotional brain keeps rational side from intellectualizing everything to death
Function together, not as separate units
He Brain vs She Brain
Males exhibit proficiency at spatial-visual tasks early, females more proficient at verbal skills throughout life (selective use of part of hemisphere?)
Injury to dominant hemisphere compromises language abilities in males more than in females (greater use of other hemisphere?)
Structural differences – Male synaptic pattern develops in preoptic nucleus of hypothalamus in response to testosterone, female pattern is the default.
Region in anterior hypothalamus involved in male-typical sexual behavior is larger in males than females or homosexual males.
Planum temporale (area of temporal lobe involved in language and auditory function) cortical granular layer neuron density higher in females.
Females have longer temporal lobe and posterior region of corpus callosum is wider.
Some neurons innervating external genitalia much larger in males than females, contain receptors for testosterone but not estrogen.
Cerebral White Matter
Deep to gray matter
Communication between cerebral areas, cerebral cortex and lower CNS
Consists mainly of tracts, classified by direction they run
Commissural fibers (commissures) (horizontal)
Connect corresponding areas between hemispheres
Corpus callosum – largest
Conduct within the same hemisphere
May be short, between gyri
Long – connect different lobes
Ascending tracts – enter from cord and lower brain centers
Descending tracts - leave cortex and run to lower centers
Internal capsule – band of projection fibers on either side of upper brain stem
Passes between thalamus and some of the basal ganglia, then radiates through cerebral white matter to cortex – corona radiata
Really nuclei, but historically called ganglia
Consist mainly of caudate nucleus and the lentiform nucleus
Lentiform nucleus = putamen + globus pallidus
Fibers make up the corpus striatum
Internal capsule fibers run past and impart a striped appearance
Amygdaloid nucleus – grouped anatomically (sits on tail of caudate nucleus) with the basal ganglia but functionally part of the limbic system
Basal ganglia receive input from other nuclei, cerebral cortex, and each other.
Centre median nucleus of thalamus
Substantia nigra of midbrain
The globus pallidus (output nucleus of the basal ganglia) and the substantia nigra project to premotor and prefrontal cortices through thalamic relays and so have indirect influence on voluntary muscle movements.
Especially slow and sustained or stereotyped motions
Impairment results in postural and muscle tone problems, tremors, abnormal slowness of movement (Parkinson’s)
Also have a role in cognition and memory
80% of diencephalon
Bilateral masses of gray matter connected by the intermediate mass (midline commissure)
Receives afferent impulses from all parts of the body and relays to appropriate area of cortex
Relays sensory impulses involved with similar functions to both sensory cortex and cortical association areas – crude recognition of pleasant vs. unpleasant sensation
Integrates some sensory input before relay to association areas
Relays hypothalamic afferents dealing with emotion and regulation of visceral activity
Relays cerebellar afferents (regulation of motor control)
Lateral dorsal – integration of sensory input and relay to cortical association areas
Lateral posterior - integration of sensory input and relay to cortical association areas
Ventral anterior – basal nuclei to cortex relays
Ventral lateral – cerebellum to cortex relay
Ventral posterior lateral – major synapse point for fibers carrying impulses from the general somatic sensory receptors
Anterior nuclear group – relays from hypothalamus (emotion and visceral function)
Pulvinar – posterior extremity of the thalamus; integration of sensory input and relay to cortical association areas
Medial geniculate body – auditory relay center
Lateral geniculate body – visual relay center
Summary of roles: mediating sensation, motor activity, cortical arousal, learning, and memory
Inferior to thalamus, caps brainstem
Mammillary bodies – paired nuclei, protrude anteriorly; olfactory relays
Infundibulum – stalk connecting hypothalamus to pituitary, runs between the optic chiasma and mammillary bodies
Main visceral control center, lots of nuclei
Autonomic control center
Controls autonomic centers in brain stem and spinal cord
Blood pressure, heart rate, contractility, digestive tract motility, respiratory rate and depth, pupil size, etc.
Center for emotional response and behavior (CERAB)
Inputs from limbic system
Perception of pleasure, fear, rage; biological rhythms, drives (sex)
Autonomic expressions of emotion – fight or flight
Body temperature regulation
Hypothalamic neurons sense blood temperature
Hypothalamic nuclei initiate cooling or heat-retention mechanisms as needed
Regulation of food intake
Hunger and satiety
Regulation of water balance and thirst
Osmoreceptors excite nuclei that trigger ADH release
Thirst centers stimulate drinking
Regulation of sleep-wake cycles
Suprachiasmatic nucleus – the biological clock times sleep wake cycle in response to light signals from visual pathways (receptors for melatonin)
Control of endocrine system functioning
Releasing and inhibiting hormones to stimulate anterior pituitary
Release of ADH (supraoptic nucleus) and oxytocin (paraventricular nucleus) from posterior pituitary
Epithalamus (roof of third ventricle)
Pineal gland - melatonin (sleep-wake cycle and mood)
Choroid plexus – manufacture of cerebrospinal fluid
Between diencephalon and pons
Ventral aspect contains cerebral peduncles
Fiber tracts containing pyramidal motor tracts
Medially, sort of, contains medial lemniscus
Spinothalamic sensory tracts - specific ascending pathways, inputs from a single type or a few related types of sensory receptor that can be localized precisely on the body surface.
Fasiculus cuneatus and fasiculus gracilis of spinal cord synapse with 2nd order neurons in the nucleus cuneatus and nucleus gracilis in medulla, continue on to terminate in the ventral posterior nuclei of the thalamus.
Between dorsal border of substantia nigra and red nucleus medially.
Dorsal aspect contains superior cerebellar peduncles
Fiber tracts connecting midbrain to cerebellum
Connects 3rd and 4th ventricles
Separates cerebral peduncles from the tectum
Surrounded by gray matter
Dorsal aspect of midbrain (the “roof”)
Periaqueductal gray matter
Nuclei that are part of the body’s endogenous pain suppression mechanism and link the amygdala (fear sensing) to the fight or flight ANS centers
Oculomotor nuclei (cranial nerve III)
Trochlear nuclei (cranial nerve IV)
Deep to cerebral peduncles
Largest nuclei in midbrain
Pigmented with melanin, the dopamine precursor
Functionally linked to basal ganglia, involved in motor control activity
Between substantia nigra and cerebral aqueduct
Pigmented – iron
Relay nuclei in descending motor pathways involving limb flexion
Reticular formation nuclei also present
Corpora quadrigemina (4)
Visual reflex centers
Coordinate head and eye movements during tracking a moving object
Involuntary head movement in response to detection of peripheral motion
Startle reflex – turning to an unexpected sound
Composed primarily of tracts
Projection fibers between cord and higher brain centers
Relay fibers between pontine nuclei and cerebellum
Connect motor cortex with cerebellum
Form middle cerebellar peduncles
Give rise to cranial nerves V, VI, and VII
Reticular formation nuclei
Pontine respiratory centers – coordinates medullary respiratory centers
Pyramidal tracts from motor cortex
Decussation just above cord
Contralateral voluntary motor control
Inferior cerebellar peduncles – dorsal connections to cerebellum
Somatic sensory tract from cord to somatosensory cortex
Inferior olivary nuclei
Relay between proprioception pathways and cerebellum
Auditory inputs (vestibulocochlear nerves)
Make up the vestibular nuclear complex
Mediate equilibrium maintenance responses
Inputs from ampullae, utricle, and sacculae
Outputs to postural and neck muscles, cerebellum, reticular formation, thalamus, and the contralateral vestibular complex
Nucleus gracilis and Nucleus cuneatus
Relays associated with medial lemniscal tract
General somatic sensory information from cord to somatosensory cortex
Visceral motor nuclei – inputs through reticular formation nuclei from hypothalamus
Rate and depth of breathing
Inputs from stomach and duodenum – distension
Tickling back of the throat
Painful injury to the genitourinary system
Chemicals (emetics) through receptors in the stomach or duodenum
Floor of the fourth ventricle (chemoreceptor trigger zone) – lies on blood side of blood-brain barrier
Regulation of hiccuping, coughing, and sneezing
Reticular formation nuclei (Raphe nucleus, medial nuclear group, lateral group)
Projections to hypothalamus, thalamus, cerebellum and cord
Anatomy of the Cerebellum
Vermis – connects hemispheres medially
Folia – gyri; all sulci are transversely oriented so gyri are parallel
Lobes – each hemisphere divided into 3 lobes by deep fissures (Primary fissure and horizontal fissure)
Anterior and Posterior Lobes
Overlapping sensory and motor maps of body
Medial portions (vermis) receive inputs from axial part of body
Influence motor activity of trunk and girdle muscles
Relay information to cerebral motor cortex
Intermediate portions of the hemisphere control distal parts of limbs and skilled movements
Lateral portions of each hemisphere receive inputs from cerebral association areas
Role in planning movements
Deep to vermis and posterior lobe
Receive inputs from equilibrium apparatus
Maintain balance and control some eye movements
Cortex of gray matter
Only cortical neurons that synapse with central nuclei of cerebellum
Mediate most output of cerebellum
Internal white matter
Branches like a tree
Known as arbor vitae because of branching pattern
Dentate nuclei – most familiar of the deep, paired masses of gray matter
Superior cerebellar peduncles
Connect to midbrain
Efferents from deep cerebellar nuclei
Connect to cerebral cortex through thalamic relays
Middle cerebellar peduncles
Connect to pons
Fibers from pontine nuclei relay voluntary motor information to cerebellum from cerebral cortex
Inferior cerebellar peduncles
Connect to medulla
Afferent sensory tracts from muscle proprioceptors and vestibular nuclei (equilibrium)
Integrates the sensory input, calculates coordination plan for force, direction, and extent of muscle contraction; prevents overshoot, maintains posture, ensures smooth, coordinated movements
Also sends output to brainstem nuclei (i.e. red nuclei of midbrain) which project to motor neurons of spinal cord
Cognitive Functions of the Cerebellum
Recognizes and predicts sequences of events to adjust for multiple forces exerted on a limb during complex movements involving several joints
Functional Brain Systems
Group of structures on medial aspect of each cerebral hemisphere and diencephalon
Anterior nuclei of the thalamus
Linked by fiber tracts (including the fornix)
Emotional brain, especially amygdala and anterior part of cingulate gyrus
Connections between lower and higher brain regions, responds to wide variety of stimuli
Hypothalamus – subject to emotional input and control of autonomic functioning; severe stress can lead to emotion-induced illness (psychosomatic illness), i.e. hypertension, irritable bowel syndrome, ulcers, and cardiac arrest
Interaction with higher cortical areas, link between feelings and conscious thought
Hippocampus and amygdala also involved in memory
System of loosely clustered neurons extending through brainstem
Found in 3 columns
Raphe nuclei (midline)
Medial (large cell) group
Lateral (small cell) group
All over -
Arousal of brain
Reticular Activating System
Receive sensory inputs from all ascending sensory tracts
Send impulses to cerebral cortex through thalamic relays
Maintains cortex in alert conscious state, enhances excitability
Filters out repetitive, familiar or weak signals
Brings attention to unusual, significant, or strong impulses
Role in learning and memory; part of “reward pathway”
Damped by sleep centers of hypothalamus, etc.
Depressed by alcohol, sleep-inducing drugs, tranquilizers
Severe injury results in unconsciousness (permanent = coma)
Damping removed by LSD and other hallucinogens
Motor arm projects to spinal cord
Helps control skeletal muscles during coarse movement of limbs
Include vasomotor, cardiac, and respiratory centers of the medulla
Higher Mental Functions
Brain Wave Patterns and the EEG
Normal Frequency Classes
Alpha waves – awake, calm, relaxed
Beta waves – higher frequency, more irregular; awake and mentally alert or concentrating
Theta waves – more irregular, seen in stage 3 NREM sleep, common in children but not normal in awake adults
Delta waves – high amplitude low frequency (< 4Hz); deep sleep, anesthesia (RAS damped), indicate brain damage in wakeful adults
Abnormal Electrical Activity of the Brain: Epilepsy
Abnormal discharge of groups of neurons
Blocks activity of other neurons during discharge
Not associated with or cause of intellectual impairment
Can be genetic or caused by injury of some kind
Blows to the head
Partial seizures result in relatively localized activity
Motor cortex origin
Localized contraction of contralateral muscles
Temporal-lobe epilepsy or psychomotor epilepsy
Originates in the limbic lobe (medial asect of cortex, borders on the brainstem)
Results in illusions (hallucinations, flashbacks, emotional outbursts, rampages) and semi-purposeful motor activity
Generalized seizures involve wide areas of the brain and loss of consciousness
Absence (Petit mal) seizures
Transient loss of consciousness (blank expression and facial twitches)
Usually seen in children
Often disappears by age 10 or so
Tonic-clonic (Grand mal) seizures
Loss of consciousness for longer periods
Tonic phase – generalized increase in muscle tone
Clonic phase – series of jerky movements
May result in broken bones, tongue biting, bowel and bladder evacuation
Result of origin of seizure in somatosensory cortex
Visual cortex – visual aura
Auditory cortex – auditory aura
Vestibular cortex – feeling of spinning
Olfactory cortex - odors
Control with anticonvulsant drugs or vagus nerve stimulator
Drugs stimulate amount of GABA (inhibitory NT)
Valproic acid – non-sedating
Phenobarbital – classic sedating
Drowsy or lethargic
Definition: Holistic information processing
Involves simultaneous activity of large areas of the cerebral cortex
Superimposed on other types of neural activity
Loss of consciousness represents impairment of brain function (except for sleep)
Syncope or fainting – ischemia due to hypotension
Coma – total unresponsiveness for an extended period of time
Sleep and Sleep-Wake Cycles
Types of Sleep
Stage 1 – Relaxation begins, vital signs normal, EEG shows alpha waves
Stage 2 – EEG becomes irregular, sleep spindles appear (short high-voltage wave burst)
Stage 3 – delta waves appear, vital signs begin to decline, SkM relaxation, some dreaming, especially nightmares
Stage 4 – delta waves
Occurs about 90 minutes after sleep begins
Paradoxical – EEG looks like alpha waves
Vital signs increase but SkM inhibited
Most dreaming occurs
Suprachiasmatic nucleus of hypothalamus receives input from retina, forms biological clock
Preoptic nucleus is the sleep-inducing center
RAS inhibition probably not important, actually mediate some parts of sleep, especially dreaming
REM begins about every 90 minutes
REM lasts 5-10 minutes in first cycle and gets progressively longer, up to about 50 minutes
Awakening occurs when neurons of the dorsal raphe nuclei of the midbrain reticular formation fire at maximal rates – this appears to be tied to a rise in core body temperature
NT changes in sleep: NE declines (regionally), serotonin levels rise
NE (released by the locus ceruleus in the pons) may induce transient paralysis of REM sleep
Importance of Sleep
Slow-wave appears to restorative
REM sleep may involve dealing with emotional crap, unlearning meaningless communications that occur during the day
Alcohol and barbituates suppress REM sleep
Benzodiazapines reduce slow-wave sleep more than REM
Requirement declines with age
Homeostatic Imbalances of Sleep
Involuntary sleep during normal waking hours
May be triggered by some pleasurable event
Last about 15 minutes, EEG looks like REM
Usually get less REM than normal at night
Involves almost all of the dominant hemisphere’s cortical association areas.
Broca’s area, Wernicke’s area, and the basal nuclei analyze input and organize output related to word sounds and grammatical structure.
These areas are surrounded by cortical areas that join them to other cortical regions that hold concepts and ideas.
Lesions to Broca’s area produce aphasia characterized by an understanding of language but difficulty with speaking and sometimes writing, typing, and sign language.
Lesions to Wernicke’s area produce aphasia characterized by difficulty understanding language and nonsensical speaking referred to as “word salad”.
Affective language areas are found in the same areas of the opposite hemisphere and are involved in emotional aspects of language (body language, tone, gestures)
Stages of Memory
Short-term memory (STM)
Preliminary step to LTM
Limited to 7 or 8 bits of information (phone number)
Long-term memory (LTM)
Ability to store and retrieve declines with age
Some sensory input selected for transfer to STM, may or may not decide to transfer to LTM
Transfer from STM to LTM affected by:
Emotional State – best when alert, motivated, aroused
Association with pre-existing information already in LTM
Automatic memory – some LTMs are formed unconsciously
Memory consolidation – file new information into existing categories already stored
Categories of Memory
Declarative (fact) memory
Related to conscious thought and language ability
Often forgotten quickly but may be filed in LTM in context
Less conscious or unconscious, noncontextual, best remembered through doing
Procedural (skills) memory
Brain Structures Involved in Memory
Declarative memory: hippocampus and amygdala (limbic system), diencephalon (thalamus and hypothalamus), ventromedial prefrontal cortex, and basal forebrain (cluster of ACh-secreting neurons anterior to the hypothalamus)
Sensory perception ® cerebral sensory cortical neurons send impulses along parallel circuits to hippocampus and amygdala ® both send information to diencephalon, basal forebrain and prefrontal cortex; Basal forebrain ® sensory cortical areas the sensory information came from
This pathway makes the perception more durable (a memory)
Retrieval from LTM by prefrontal cortex
Nondeclarative memory (habit system): Sensory input ® Cerebral cortex ® corpus striatum ® brain stem nuclei, promotes motor response
Cerebellum also involved for conditioning of voluntary muscle contractions
Mechanisms of Memory
Hard to study, but probably involves the glutamate – NMDA – calcium – NO long term potentiation pathway mentioned earlier
Activation of genes that code for synaptic proteins in postsynaptic cells includes cAMP-CREB and BDNF
Protection of the Brain
Meninges – 3 connective tissue membranes covering the CNS
Cover & protect the CNS
Protect blood vessels & enclose venous sinuses
Partition the skull
Outermost, consists of 2 layers of fibrous connective tissue (periosteal layer attached to inside of skull – fused to periosteum, present in skull only, meningeal layer covering the brain and spinal cord, forms the dural sheath of the spinal cord in the vertebral canal).
Layers separate in brain, enclose dural sinuses, which collect venous blood from the brain and send it to the internal jugular veins.
Dural septa - Meningeal layer extends inward to form partitions subdividing the cranial cavity and limiting movement of the brain inside the skull.
Falx cerebri – fold in the longitudinal fissure, attached to crista galli (ethmoid bone) anteriorly
Falx cerebelli – inferior posterior continuation of falx cerebri, folds along the vermis
Tentorium cerebelli – folds into transverse fissure between cerebral hemispheres and cerebellum
Deep to the dura mater, separated by the subdural space, which is filled with serous fluid.
Consists of fine elastic connective tissue with weblike extensions inward to attach to the underlying pia mater.
Subarachnoid space (between arachnoid and pia mater) is filled with CSF and contains the largest blood vessels of the brain.
Projections that extend exteriorly into the superior sagittal sinus form arachnoid villi, which return CSF to the venous blood
Fine connective tissue, highly vascular, clings tightly to surface of the brain
Brain and spinal cord float in CSF, which reduces pressure of brain against skull and keeps brain from collapsing under its own weight.
Cushions CNS against trauma.
Nourishes brain and spinal cord
Carries chemical signals from one area of brain to another (hormones, sleep- and appetite-controlling molecules)
Filtered from plasma at the choroid plexuses
Clulsters of thin-walled, permeable capillaries surrounded by pia mater and ependymal cells in the ventricles.
Tissue fluid is filtered continuously from blood
Ependymal cells modify filtrate by pumping only specific ions into CSF and removing waste products and unnecessary solutes.
Water follows solutes by osmosis, across ependymal cells and into the CSF in the ventricles.
Average adult formation of CSF is about 500 ml per day.
Less protein, Ca++, and K+ than plasma, more Na+, Cl-, and H+.
CSF moves through ventricles, and from fourth ventricle moves through median and lateral apertures into subarachnoid space or inferiorly into the central canal of the spinal cord.
Cilia of ependymal cells wave to circulate CSF, which baths surface of CNS in subarachnoid space and returns to venous circulation at the arachoid villi.
Continuous endothelium of capillary walls, endothelial cells joined by tight junctions.
Thick basal lamina around each capillary.
Regulated by foot processes of astrocytes, stimulate tight junction formation between endothelial cells.
Maintain relatively constant environment in CNS by only allowing nutrients like glucose, essential amino acids, and some elecrolytes passage (by facilitated diffusion) while blocking bloodborne metabolic wastes, proteins, some toxins, and most drugs.
Some nonessential amino acids and K+ moved by active transport from brain into blood.
Fat soluble substances (lipids, O2, CO2, some drugs, and alcohol) pass through easily.
Absent at vomiting center (brainstem) and hypothalamus, where blood contents need to be sampled.
Homeostatic Imbalances of the Brain
Traumatic Brain Injuries
Coup and contrecoup
No permanent neurological damage, symptoms include dizziness, confusion, maybe momentary loss of consciousness, headache
Tissue destruction, may be the result of repeated insult (lots of concussions); symptoms depend upon area affected
Brainstem contusions can cause coma; damage to RAS
Compression of tissue
Water uptake by tissues
Treat with anti-inflammatories
Cerebrovascular Accidents (CVAs)
Most common NS disorder
3rd leading cause of death in the US
Ischemia leading to anoxia, glutamate, etc.
Blockage of arteries
Compression of tissue
TIAs (transient ischemic attacks)
Last 5-50 minutes
Temporary numbness, paralysis, impaired speech, higher level processing
Partial blockage due to thrombosis, vasospasm, or embolism
May be predictive of stroke to come
Treat with clot busters (tPA, streptokinase) or clotting inhibitors (aspirin, warfarin/Coumadin)
Treatment within 3 hours increases chances of survival without permanent damage by 50%
Degenerative Brain Diseases
Progressive degeneration of cholinergic neurons in cortex and hippocampus
Neurofibrillar tangle formations
Mutated tau protein
Mediates microtubule formation
Mutation results in neurofibrillary tangles within neurons
Senile plaque formation
Cells and fibers surrounding a core of b-amyloid
Amyloid Precursor Protein normally broken down by both secretory pathways and lysosomal degredation
Short-term memory loss
Degeneration of dopamine producing neurons in substantia nigra – project to corpus striatum (basal nuclei).
Results in tremor, slowed movement, rigidity.
Treated with l-dopa (crosses blood-brain barrier, is converted to dopamine in CNS) and drugs that enhance the effects of dopamine.
When response to drugs declines deep brain stimkulation with electrode implants can inhibit tremors.
Gene therapy to enhance GABA secretion could inhibit abnormal brain activity and the use of stem cells has shown promise.
Autosomal dominant genetic disorder that manifests in middle age, causes accumulation of mutant huntingtin protein in brain, causing degeneration of basal nuclei followed by degeneration of cerebral cortex.
Early signs are involuntary "dancing" movements (chorea). Cognitive function degenerates later in the disease, which is progressive and fatal, usually within 15 years of onset of symptoms.
Treatments are designed to inhibit dopamine activity and stem cell implants may offer some hope in the future.
The Spinal Cord
Gross Anatomy and Protection
Foramen magnum to 1st or 2nd lumbar vertebra (just inferior to ribs)
Conus medullaris – tapered end of cord
Nerve roots extend to appropriate level before exiting: Cauda equina
Dura mater – spinal dural sheath
Not attached to vertebrae
Between dura and inner vertebral wall
Filled with fat and veins
Subarachnoid space between arachnoid and pia
Filled with CSF
Extends to S2 with dura
Lumbar puncture – done in subarachnoid space in meningeal sac inferior to conus medullaris, no cord, roots located laterally to exit at appropriate intervertebral foramina
Pia extends to coccyx and attaches to anchor cord (filum terminale)
Lateral extensions of pia anchor cord to vertebra throughout length – denticulate ligaments
Cervical and lumbar – site of nerves that serve upper and lower limbs
Spinal Cord Cross-Sectional Anatomy
Flattened from anterior to posterior
Two grooves on surface
Anterior median fissure
Posterior median sulcus
Gray Matter and Spinal Roots
H - or butterfly shaped, joined by gray commissure
Dorsal horns – posterior projections
Interneurons receiving sensory input
Sensory neurons have cell bodies in dorsal root (dorsal root ganglion)
Receive both somatic sensory and autonomic (visceral) sensory input
Ventral horns – anterior projections
Nerve cell bodies of somatic motor neurons
Axons exit via ventral roots to SkM
Amount of gray matter corresponds to amount of muscle innervated
Lateral horns – present in thoracic and superior lumbar segments
Autonomic motor neurons of the sympathetic division
Serve visceral organs
Axons exit via ventral roots
Composed of nerve fibers that run in 3 directions: Ascending, descending, and transverse
Divided into columns or funiculi
Posterior, lateral, or anterior
All major spinal tracts are part of multi-neuron pathways
Contain spinal cord neurons, and parts of peripheral neurons and brain neurons
Most pathways cross over at some point
Most consist of chains of 2 or 3 neurons
Most exhibit somatotopy
All pathways and tracts are paired
Ascending Pathways to the Brain
Typically chains of 3 neurons
Three main pathways on each side of spinal cord: specific (dorsal column-medial lemniscal), nonspecific (spinothalamic), and spinocerebellar.
Specific Ascending Pathways (dorsal column-medial lemniscal system)
Transmit to sensory cortex: conscious interpretation
Found in the posterior funiculus (dorsal white column)
Fasciculus cuneatus and fasciculus gracilis
Synapse with nucleus cuneatus and nucleus gracilis in medulla oblongata
Medial lemniscal tracts
Originate in the medulla, synapse with ventral posterior nuclei in the thalamus and with reticular formation nuclei.
Carry sensory input concerning fine touch, pressure receptors, joint proprioceptors
Discriminative touch and conscious prorioception
Can localize source of input precisely on body surface
Nonspecific Ascending (anterolateral) Pathways (spinothalamic)
Lateral and anterior spinothalamic tracts
Synapse with reticular formation nuclei, and thalamic nuclei
Carry sensory input concerning pain, temperature, deep pressure, coarse touch
Ascending Spinocerebellar Tracts
Transmit proprioceptor information to the cerebellum, no conscious perception
Anterior and posterior spinocerebellar tracts
Terminate in cerebellum
Progressive deterioration of posterior white matter tracts and associated dorsal roots
Caused by syphilis
Poor muscle coordination and unstable gait due to destruction of joint proprioceptor tracts
Invasion of sensory roots by bacteria causes pain, pain passes when dorsal root is completely destroyed
Projection – phenomenon where brain refers sensations to their usual point of stimulation no matter where they arise (can directly stimulate cortex and think you “felt” it on the surface of the skin)
Descending (Motor) Pathways and Tracts
Direct (Pyramidal) Tracts
Originate as pyramidal neurons in precentral gyrus, send impulses through brain stem (corticospinal tracts) and synapse with interneurons or ventral horn motor neurons in spinal cord.
Both tracts transmit motor impulses to spinal cord neurons that activate contralateral skeletal muscles.
Indirect (Extrapyramidal) System
Brain stem motor nuclei and all motor pathways except pyramidal pathways.
Most receive projections from and are influenced by pyramidal tract neurons – not really extrapyramidal, more multineuronal.
Complex, multisynaptic, involved in reglation of:
Axial muscles that maintain blance and posture
Muscles controlling coarse limb movements
Head, neck, and eye movements that track objects in visual field
Most activities depend on reflex activity
Originates in superior colliculus of midbrain – coordinates head and eyes toward moving visual targets.
Originates in vestibular nuclei in medulla, maintains muscle tone, activates ipsilateral limb and trunk extensors and head to maintain balance during standing and moving.
Originates in Red nucleus of midbrain, controls some upper limb movement (flexors).
Originates in reticular formation nuclei of pons and medulla, controls muscle tone, visceral motor functions, may control most unskilled movements.
Spinal Cord Trauma and Disorders
Spinal Cord Trauma
Damage causes either sensory loss or motor function loss.
Damage to ventral root or ventral horn cells stops impulses from reaching muscles served.
No movement, atrophy
Only upper motor neurons of primary motor cortex damaged.
Spinal motor neurons, muscles stimulated by spinal reflex activity
No voluntary control but don’t atrophy as much (become shortened)
Total motor and sensory loss in regions inferior to site of damage
Paraplegia – transaction between T1 and L1, both lower limbs affected
Quadriplegia – damage in cervical revion, all four limbs affected
Hemiplegia – paralysis of one side only, usually due to brain injury
Transient period of functional loss following traumatic cord injury.
Immediate depression of all reflex activity below site of injury: bowel and bladder reflexes stop, BP drops, all muscles are paralyzed and insensitive.
Function usually returns within a few hours, if not by 48 hours paralysis is usually permanent.
Transmitted by ingestion of fecally contaminated water.
The virus first invades lymph nodes of the neck and small intestine.
Stiffness of the back and neck
Occasionally paralysis (less than 1%)
Viremia and spinal cord involvement may follow, including destruction of ventral horn motor neurons.
Death may occur by respiratory failure or cardiac arrest depending on muscles affected.
Most cases are mild or asymptomatic. Vaccines keep the incidence low in the US.
Salk (IPV) (1954) - Formalin-inactivated virus; Requires boosters.
Sabin (OPV or TOPV) (1963) - Contains three strains of live virus – trivalent; Administered orally, no boosters.
Postpolio Syndrome – Experienced by some survivors of polio epidemic of 40’s and 50’s.
Extreme lethargy, musclar burning pains, progressive muscle weakness and atrophy.
May be due to normal loss of neurons in aging with inability to recruit nearby neurons to compensate for losses (already recruited these neurons to compensate for loss of neurons due to infection).
Amyotrophic Lateral Sclerosis
Progressive destruction of ventral horn motor neurons and pyramidal tract fibers.
Results in loss of ability to speak, swallow, and breathe, with death occuring typically within 5 years.
Idiopathic in 90% of cases although may be due to glutamate excitotoxicity, autoimmune reactions, or a combination.
Riluzole inhibits glutamate release, only drug developed in last 50 years to treat ALS.
Diagnostic Procedures for Assessing CNS Dysfunction
Clot busters for stroke (tPA)
Cerebral angiography can show location of clot so tPA can be applied directly, also used for patients who have had warning strokes or TIAs.
Ultrasound – cheaper and less invasive than angiography
Developmental Aspects of the Central Nervous System
Arises from ectoderm of dorsal midline - 3rd week of pregnancy
Invaginates, forms the neural groove flanked by neural folds.
Superior edges fuse over deepening groove to form the neural tube. Some neural fold cells migrate laterally and form the neural crest.
Neural Tube – by 4th week
Detaches from surface ectoderm, differentiates into brain rostrally and spinal cord caudally.
Neuroblasts migrate outward from the neural tube and form the alar plate dorsally and the basal plate ventrally by the 6th week.
Basal plate neuroblasts form motor neurons.
Alar plate neuroblasts form interneurons, which, along with some basal plate neuroblasts form the white matter of the spinal cord.
Formed from neural fold cells
Gives rise to sensory neurons (dorsal root ganglia) and some autonomic neurons.
Cerebral palsy - brain damage causes voluntary muscles to be paralyzed or poorly controlled.
Spasticity, speech difficulties and other motor difficulties are seen and may be accompanied by visual impairments, seizures (about half), mental retardation (about half), and deafness (about one third).
Cerebal palsy is not progressive but is irreversible. Possible causes include lack of oxygen during delivery or maternal exposure to radiation, alcohol and other drugs, infection, or smoking during pregnancy.
Anencephaly - neural folds don't fuse rostrally, causing the cerebrum and part of the brain stem to be lacking (anencephaly = "without brain").
There is no ability to see, hear, process other sensory input, initiate voluntary muscle movement, or think. Death occurs soon after birth.
Spina bifida - due to incomplete formation of the vertebral arches (laminae and spinous processes are missing on at least one vertebra).
Usually occurs in the lumbosacral region. Neural deficits are seen in severe cases.
Spina bifida occulta is the least serious (and most rare) type, involves one or a few vertebrae, and causes no neural problems. A small dimple or tuft of hair may be seen over the site but there are no other external manifestations.
Spina bifida cystica is more common and severe, with a saclike cyst protruding dorsally from the spine.
Meninogoceles contain meninges and cerebrospinal fluid.
Myelomeningoceles contain portions of the spinal cord and spinal nerve roots.
Larger cysts with more neural structures cause greater neurological problems, whith may include bowel incontinence, bladder paralysis, lower limb paralysis and continual infections. 90% of cases are accompanied by hydrocephalus.
Inadequate amounts of folate in the maternal diet have been implicated in about 70% of cases in the past but the incidence has dropped significantly since mandatory supplementation of bread, flour, and pasta products started.