Key differences in CNS fluid barriers

(BBB,BCSFB,CSF-interstitial)

• BBB - seperates the blood plasma from brain interstitial fluid (not present at circumventricular organs)
• BCSFB - seperates blood plasma from CSF (at the choroid plexus)
• CSF-interstitial fluid barrier - only a barrier at the tanycytes of the circumventricular organs 
• CSF and interstitial fluid are not the same, as dictated by simple diffusion

Plasma vs CSF conditions 

(significant differences)

• [K⁺]_plasma:CSF = 4.6:2.9mM
• [Ca²⁺]_plasma:CSF = 5.0:2.5
• [Amino acids]_plasma:CSF = 2.3:0.8
• _{pH plasma:CSF} = 7.41:7.31
• [Protein]_plasma:CSF = 7000mM:28mM

Internal capsule

(location, fibres carried)

• Situated in inferomedial part of the cerebral hemispheres
• Separates caudate nucleus and thalamus from the putamen and globus pallidus
• Carries fibres to and from the cerebral cortex - corticospinal tract from primary motor cortex to the lower motor neurons of spinal cord
• Internal capsule also carries thalamic tracts to frontal lobe, the lentiform fibres (from putamen and globus pallidus) to the caudate nuclei, cortex fibres to striatum and sensory fibres from thalamus, optic radiation and acoustic fibres

Optic radiation

(location, fibres carried)

• White matter tract from LGN to visual cortex
• Separated into the upper division projecting to cuneus (banks of calcarine fissure) and containing inputs for the inferio quadrants of visual field
• Lower divison follows Meyer's loop to terminate on lingual gyrus and contains superior visual field quandrants

Cerebral peduncles

(location, fibres carried)

• Front of midbrain - arise from front of pons
• Carry ascending sensory and descending motor tracts from cerebrum to pons 
• Receive input from internal capsul - corticopontine within inner and outer third, cerebro-bulbar and corticospinal tracts in central third

Caudate nucleus

(location, overview of function)

• Caudate nucleus (part of dorsal striatum with putamen) is divided from putamen by internal capsule laterally, is a C shape with wider head and tapering body. 
• Caudate nucleus receives fibres from SNc and association cortices to play a role in motor and cognitive functions

Putamen 

(Location and overview of function)

• Putamen - round structure at the base of forebrain and is most laterally of basal ganglia- connection with SN and globus pallidus to regulate movement and influence learning - forms lenticular nucleus with globus pallidus

Globus pallidum

(location and overview of function)

• Globus pallidus is part of telencephalon and makes direct contact with the substantia nigra. 
• Divided into inner and outer part by the medial medullary lamina, and regulates voluntary movement

Subthalamic nuclei

(location and overview of function)

• Subthalamic nucleus - small lens shaped nucleus below thalamus. Receives input from GP and targets many of the basal ganglia nuclei - function as central pacemaker of basal ganglia with the GPe

Substantia nigra

(location and overview of function)

• Substantia nigra is inferior to SN, and is divided into pars reticulata and pars compacta. Pars reticulata bears resemblance to GPi and conveys final processed signals to thalamus and superior colliculus, pars compacta contains dopaminergic neurons. Thought to be roles in motor control and learned responses to stimuli - role in reward through dopaminergic axis

Nucleus accumbens 

(location and overview of function)

• Rostral to preoptic area of hypothalamus - collectively forms the ventral striatum with the olfactory tubercle
• Divided into a core and a shell - different morphology and function
• Input from the prefrontal cortex, basolateral amygdala, hippocampus, thalamus and VTA
• Output to the basal ganglia (pallidum), SN, reticular formation of pons
• Shell - cognitive processing of reward - pleasure centre
• Core - cognitive processing of motor function related to reward and reinforcement

Nucleus of the thalamus 

(location, function)

• Dorsal area of diencephalon
• Divided into nuclei - superiorly the anterior nuclear group and medial dorsal nucleus. Inferiorly, ventral nuclear group (containing ventral anterior, lateral, posteriolateral and posteromedial nucleus) and lateral nuclear group. Below these, are the smaller lateral geniculate nucleus and medial geniculate nucleus
• Connections by mammillo-thalamic tract to hippocampus, connected to cortex by thalamocortical tract, and innervated by sensory pathway (spinothalamic tract) from the spinal cord
• Function - gateway, input from sensory systems relyed to cortex, important role in regulation of sleep and wakefullness, motor processing network with cerebellum and basal ganglia

Hypothalamus - nuclei

(regions, areas and nuclei)

• Located under the thalamus
• Divided into regions, areas and nuclei:
•  anterior region contains preoptic area (preoptic nucleus), medial area (medial preoptic nucleus, supraoptic nucleus, paraventricular nucleus, anterior hypothalamic nucleus, suprachiasmatic nucleus) and lateral area (lateral nucleus). 
• Tuberal region contains medial area (dorsomedial hypothalamic nucleus, ventromedial nucleus and arcuate nucleus) and lateral area (lateral nucleus and lateral tuberal nuclei). 
• Posterior region contains medial (mammillary nuclei, posterior nucleus) and lateral (lateral nuclei and tuberomammillary nucleus)

Hypothalamus 

(function of regions)

• Anterior - release of gonadotrophins, vasopressin/oxytocin release, TRH/CRH release, thermoregulation, circadian rhythm, orexin neurons
• Tuberal - blood pressure, HR, GI control, satiety, GHRH release, prolactin inhibition, orexin nuerons
• Posterior - memory, blood pressure, vasopressin release, arousal, feeding, learning, sleep

Mammillary bodies

(location and function)

• Ends of anterior arches of fornix - underside of the brain
• Relay of impulses from amygdala and hippocampus to the thalamus
• Importance in recollective memory and spatial memory

Pineal gland 

(location and function)

• Located at the posterior aspect of the thalamus
• Receives sympathetic input from the superior cervical ganglion and parasympathetic innervation from pterygopalantine and optic ganglion 
• Produces melatonin during darkness - regulation of day/night cycles

Amygdala

(location and function)

• Deep and medial aspect of temporal lobe
• Projections to hypothalamus, thalamus, VTA and facial/trigeminal nerve nuclei
• Involved in emotional learning as well as positive conditioining. Memory consolidation and modulation.

Medullary pyramids

(location and function)

• Ventral portion of medulla 
• Contain the motor fibres of the corticobulbar and corticospinal tracts - decussation and caudal end

Dorsal column nuclei

(location and function)

• Cuneate (lateral) and gracile (medial) nuclei - at junction of spinal cord and the medulla 
• Contain secondary neurons from dorsal column-medial lemiscus pathway
• Sends axons to form the internal arcuate fibres that decussate to form the medial lemniscus

Pontine nuclei

(location and function)

• Corticopontine fibres from primary motor cortex travel to ipsilateral pontine nucleus - found ventrally in pons 
• Projects pontocerebellar tract to middle cerebellar peduncle 
• Pontine nuclei is extension of the arcuate nucleus within the medulla

Inferior olivary nucleus

(location and function)

• Located in the olivary body 
• Fibres decussate and ascend into the cerebellum via the inferior peduncle (climbing fibres)
• Receives fibres from the deep cerebellar nucleus

Olivary body

(location and function)

• Anterior surface of the medulla - lateral to the pyramid
• Inferior olivary nucleus is part of the cerebellar system 
• Superior olivary nucleus is part of the pons and aids in the perception of sound

Midbrain

(structure and function)

• Comprises the tectum, tegmentum, cerebral aqueduct and cerebral peduncles
• Considered part of the brain stem - dopamine production in SN and VTA part of excitation, motivation and habituation
• Tectum at dorsal part of midbrain - divided into the superior colliculus (visual processing) and inferior colliculus (auditory processing)
• Tegmentum located between ventricular system and basal/ventral structures - network of neurons involved in homeostatic and reflexive pathways - contains red nucleus, cerebral aqueduct, PAG and parts of the substantia nigra and VTA

Periaqueductal grey 

(location and function)

• Located around the cerebral aqueduct of tegmentum
• Contains enkephalin neurons
• Projection onto raphe serotonin neurons to release into dorsal horn to produce analgesia by releasing endogenous opioids

Locus coeruleus

(location and function)

• Posterior area of rostral pons - contains noradrenergic neurons
• Innervation of spinal cord, brainstem, cerebellum, hypothalamus, amygala and cortex
• Receives afferents from hypothalamus and cingulate gyrus 
• Function inarousal, attention, cogntive control, emotional control and posture

Cranial nerve nuclei in midbrain

(name and division of nerve)

• Mesencephalic trigeminal nucleus (V) - sensory
• Trochlear nucleus (IV) - motor
• Oculomotor nucleus (III) - motor
• Edinger-Westphal nucleus (III) - visceromotor

Cranial nerve nuclei in pons

(name and division of nerve)

• Cochlear nuclei (VIII) - sensory
• Vestibular nuclei (VIII) - sensory
• Salivary nucleus (IX, VII) - visceromotor
• Facial nucleus (VII) - motor
• Adbucens nucleus (VI) - motor 
• Trigeminal motor nucleus (V) - motor
• Main trigeminal nucleus (V) - sensory 

Cranial nerve nuclei in medulla

(name and division of nerve)

• Hypoglossal nucleus (XII) - motor
• Dorsal motor nucleus of vagus nerve (X) - visceromotor
• Nucleus ambiguus (IX, X, XI) - motor
• Solitary nucleus (VII, IX, XI) - sensory
• Spinal trigeminal nucleus (V) - sensory

Corticospinal tract

(passage and innervation)

• Originates primary motor cortex and premotor frontal areas
• Travel through posterior limb of internal capsule and enter cerebral peduncles
• Pass from pons to the medulla, forming the pyramids with the corticbulbar tract
• Lateral corticospinal tract decussate in the spinal cord and innervate limbs and digits, anterior corticospinal neurons do not decussate, and innervate trunk muscles

Corticobulbar tract

(passage and innervation)

• Originates in the primary motor cortex and passes through the genu of internal capsule
• Passes through cerebral peduncles and into the pyramids
• The upper motor neurons of the tract terminate on the motor neurons of the brain stem nuclei
• Innervation of the cranial motor neurons bilaterally - except lower facial nuclei (only unilaterally below eyes) and unilateral innervation of cranial nerve XII

Dorsal columns, internal arcuate fibres and medial lemniscus

(passage and innervation)

• Posterior area of white matter within the spinal cord
• Made up from the gracile fasciculus and cuneate fasciculus
• Ascends containing touch and proprioceptive input to reach the gracile and cuneate nuclei, where the fibres begin to decussate and become the internal arcuate fibres
• Once decussated, the fibres become part of the medial lemniscus within the pons and midbrain, located in the dorsal, medial area and innervating the ventral posterolateral nucleus of the thalamus

Lateral lemniscus

(path and innervation)

• Carries information from the cochlear nucleus  to brainstem nuclei and contralateral inferior colliiculus
• Neurons from the cochlear nucleus decussate to innervate the superior olivary complex, from which they course through the lateral lemniscus in the dorsal aspect of the pons to innervate the inferior colliculus

Spinoreticular, spinomesencephalic and spinothalamic tracts

(path and innervation)

• Spinoreticular tract begins with first order neurons which synapse on second order neurons in dorsal horn of the spinal cord
• Immediate decussation (anterior white commissure) to anterolateral column - travel up spinal column 
• Termination in the brainstem at the medullary-pontine reticular formation to transit pain stimuli for autonomic responses
• Spinomesencephalic tract also travels through the anterolateral tract, to terminate on the inferior and superior colliculi
• The spinothalamic tract follows the same path, passes through the rostral centromedial medulla then moves dorsally to synapse in nuclei of the thalamus. From there, fibres are sent to the cingulate cortex, somatosensory cortex and the insular cortex

Medial longitudinal fasciculus

(path and innervation)

• Pair of crossed fibre tracts and carrie fibres near the middle of the brainstem (by PAG)
• Connections of oculomotor nerves, trochlear nerve and abducens nerve 
• Carries information about movement of eyes
• Connects cranial nerve nuclei III, IV and VI together, and integrates movements to produce saccadic eye movement and vestibulo-ocular reflexes

Spinocerebellar tract

(path and innervation)

• Axonal fibres from spinal cord to ipsilateral cerebellum
• Conveys information from golgi tendon organs and muscle spindles about muscle length 
• First order neurons through dorsal horn - synapse and pass up through the tracts on the lateral largins of the spinal cord

Pontocerebellar fibres 

(path and innervation)

• Second order neurons of corticopontocerebellar tract that decussate within pons and run within the middle cerebellar peduncles to the contralateral cerebellar nuclei

Superior cerebellar peduncle

(path and innervation)

• Paired white matter structure 
• Mainly efferent fibres of the cerebellothalamic tract and cerebellorubral tract
• Carries afferent ventral spinocerebellar tract, trigeminothalamic fibres and tectocerebellar fibres

Spinal tract of the trigeminal

(path and innervation)

• Pain and temperature sensation from face (V, VII, IX, X) enters the brainstem and sent to spinal-trigeminal nucleus - known as the spinal tract of the trigeminal nucleus 
• It is analogous to and continuous with Lissauer's tract as it passes through brainstem

Posterior commissure

(path and innervation)

• White fibres crossing midline on the dorsal aspect of upper end of cerebral aqueduct
• Mediates the consensual pupillary light reflex as it interconnects the pretectal nuclei, and gives from the nucleus of the posterior commissure, posterior parts of the thalamus and the superior colliculus

Cerebellar peduncles

(names and major tracts)

• Superior - output to cerebral cortex, via thalamic nuclei to upper motor neurons from the deep cerebellar nuclei
• Middle - Input, which themselves recieve input from the cerebellum, and course via the transverse pontine fibres to the cerebellum - afferent fibres are grouped into three afferents with different terminations within the cerebellum
• Inferior - input from vestibular nuclei, spinal cord and tegmentum. Output to vestibular nuclei and reticular formation. Input from the inferior olivary nucleus (modulatory for whole cerebellum)

Cerebellar gross anatomy

(major lobes and structures)

• Main body of cerebellum divided by vermis medially, and hemispheres laterally
• Hemispheres are divided in the coronal plan by the primary fissure (anterior) and horizontal fissure (posterior), giveing a anterior and posterior lobe
• The flocculonodular is divided from main body of cerebellum by the posterior fissure, and consists of nodulus medially and flocculus laterally

Cerebellar nuclei

(names and connections)

• Dentate - largest and most laterally of nuclei. Recieves input from premotor and supplementary motor cortices via the pontine nuclei. Efferent fibres via superior cerebellar peduncle to red nucleus and contralateral VA/VL thalamus - modulation of planning, initiation and control of movement 
• Interposed nucleus - (composed of the globose and emboliform nucleus) - lateral to fastigal nucleus in the paravermis. Afferents from anterior lobe of cerebellum and cuneocerebellar/spinocerebellar tract and efferents to superior cerebellar peduncle to red nucleus. Co-ordination of agonist/antagonist paired muscles
• Fastigial nucleus - most medial - rostral FN receives input from vestibular nuclei and interprets movement of the body through space (anti-gravity muscle, standing and walking control), caudal FN - saccadic eye moveemtns - output from oculomotor vermis to cFN and relayed to cortical areas associated with eye fields

Spinal cord termination level

(adult and neonates)

• Adults - L1/2
• Neonates - L2/3

Dorsal horn internal organisation

(zones and neuron synapses)

• Posteromarginal zone (lamina I) - most dorsal aspect of dorsal horn. Input from Lissauer's tract and relays non-modulated pain and temperature information 
• Substantia gelatinosa (lamina II) - one point of synapse of first order spinothalamic neurons. Contains μ and κ opioid interneurons, allowing pain modification. Termination of C fibres - slow conducting pain sensation. Some Aδ fivres relaying fast, localised pain sensation 
• Nucleus proprius (laminae III and IV) - first synapse of spinothalamic tract - pain and temperature sensation from peripheral cells - project to deeper laminae, posterior column nuclei and midbrain/thalamus/hypothalamus. 

Ventral horn organisation

(zones and synapses)

• Dorsomedial - extensors of the trunk
• Ventromedial - extensors of the trink
• Ventrolateral - flexors of arm/thigh (more dorsal), extensors of arm/thigh (more ventral)
• Dorsolateral - flexors of forearm/leg (more dorsal), extensors of forearm/leg (more ventral)
• Retrodorsolateral - flexors of the hand/foot (more dorsal), extensors of the hand/foot (more ventral)

Lateral horn organisation

(zones)

• Autonomic synpathetic preganglionic visceral motor nueron synapses within the lateral horn
• Clarke's column - interneurons in medial lamina VII - major relay of unconcious proprioception - synapse of primary neurons from muscle spindles and Golgi tendon organs

Corticospinal tract

(function and lesion)

• Lateral corticospinal tract90% of upper motor nuerons decussate (90%, other 10% decussate at corresponding level in spinal cord) in medulla and course through lateral corticospinal tract to control limb and digits (located between the dorsal and ventral horns)
• Anterior corticospinal tract - do not decussate - course at ventromedial aspect of the spinal cord to synapse and innervate trunk muscles
• Lesion - if after decussation, loss of function on corresponding side of the body. Loss of all (initially) motor control, all can be regained except fine motor control 

Dorsal columns

 (function and lesion)

• First order sensory neurons course through dorsal column before synapsing in dorsal column nuclei and decussation of medial lemniscus
• Lateral to medial - cuneate fasciculus carrying cervical and some thoracic input (from arms), gracile fasciculus carrying thoracic, lumbar and sacral input (from legs)
• Lesion - loss of tactile sensation, or movement sense in sites below lesion on ipsilateral side

Anterolateral tract

(function and lesion)

• Lateral spinothalamic tract is found just lateral to dorsal horn. Orientated with most inferior spinal levels (e.g. sacral) being most lateral. Neurons confering information from free nerve endings (temperature and pain) enter posterior horn and synapse in laminae I and Vafter ascending around two levels. Decussation in anterior white commissure and ascend in contralateral lateral spinothalamic tract.
• Anterior spinothalamic tract - just lateral to the anterior corticospinal tract - conduction of soft nociceptive information. Synapse and decussate in same manner as the lateral spinthalamic tract.
• Lesion - if brain stem or higher, deficits of pain, touch and proprioception are all contralateral. With spinal cord lesion, pain sensation will be contralateral (due to decussation in spinal cord) while touch sensation is ipsilateral

Spinocerebellar tract

(function and lesions)

• Transmission of proprioceptive information first order sensory neurons from Golgi tendon organs and muscle spindles which synapse on secondary neurons within the dorsal horn.
• Posterior tract - neurons synapse within the Clarke's column, then course ispilaterally through the posterior spinocerebellar tract to innervate the cerebellum (body and legs)
• Anterior tract - neurons synapse in Clarkes column and decussate through the anterior white commisure to innervate the superior cerebellar peduncle of the rostral pons (body and legs)
• Cuneocerebellar tract - similar to posterior tract, located anteriorly and conveys information from ipsilateral arms

Posterolateral tract

(function and lesion)

• Located at the tip of dorsal column 
• Contains second order axons from dorsal root ganglion cells carrying course touch and pressure information 
• Allows C and Aδ fibres to ascend or descend several layers before synapsing and decussating

Vestibulospinal tract

(function and lesion)

• Located at most medial and ventral aspect of the spinal cord
• Medial - Descending extrapyramidal motor neurons originating in the medial vestibular nucleus and terminate on interneurons neurons of the laminae VII and VIII of the spinal cord to innervate the muscles that support the head
• Ventral - pass through the anterior portion of lateral funiculus (between dorsal and ventral horns) to innervate muscles of the body either through interneurons as above or directly on α motor neurons.
• Damage - swaying with closed eyes to ipsilateral side of damage

Reticulospinal tract

(function and lesion)

• Medial, and just ventral to central canal of spinal cord
• Innervation of anti-gravity extensor muscles (medial) and inhibition of the same muscles (lateral
• Course from pontine reticular formation (medial) and medullary pontine formation (lateral) and synapse on neurons within laminae VII and VIII to facilitate and inhibit voluntary movement
• Damage below red nucleus - causes decerebration (rigidity, unopposed extension of head and limbs)