Neuro 3000 Exam 3 OSU M

The Central Nervous System (CNS)

- encased in bone

- made up of brain and spinal cord

The Peripheral Nervous System (PNS)

- all the parts outside the CNS

- Somatic and Autonomic Nervous System

CNS and Brain

- cerebrum

- cerebellum

- brain stem

- spinal cord

Cerebrum

- two hemispheres

- hemispheres receive input from and control contralateral side

Cerebellum

- contains as many cells as cerebrum

- many connections to cerebrum & spinal cord

- sides receive input from and control ipsilateral side

Brain stem

- relay center

- regulates body temperature, breathing, & consciousness

Spinal cord

- encased in vertebral column

- spinal nerves are NOT part of CNS, part of PNS

Pyramidal Decussation

point at the junction of the medulla and spinal cord where the motor fibers from the medullary pyramids cross the midline. The fibers then continue into the spinal cord primarily as the corticospinal tract

Anterior/Rostral

Front

Posterior/Caudal

Rear

Lateral

side

Medial

middle

Dorsal

Top (back)

Ventral

bottom (belly)

Superior

above another structure

Inferior

below another structure

Superficial

close to the surface

Deep

further from the surface

sagittal plane

divides into left and right

Transverse plane

-

Horizontal plane

-

Gyri

ridges of the brain

Sulci

the valleys in between ridges

- central sulcus

- lateral sulcus/Sylvian fissure

- Parieto-Occipital sulcus

Fissure

deeper than a sulcus; separates major divisions

Grey matter (cortex)

made up of cell bodies of neurons

White matter

made up of myelinated axons

Nucleus

a mass of neurons, usually deep in the brain

Dorsal and ventral roots of spinal cord

- while in the CNS, they are myelinated by oligodendrocytes and protected by meninges

- in PNS, Schwann cells take over both functions

Dorsal roots

allows sensory neurons to enter the spinal cord

Ventral roots

allows motor neurons to exit the spinal cord

somatic nervous system

voluntary behaviors

Autonomic (visceral) nervous system

- supplies motor & sensory innervation to structures not under voluntary control

- has sensory and motor (smooth muscle) functions

- axons innervate organs, glands, blood, vessels

Preganglionic neurons in sympathetic system

emanate from the thoracic and anterior lumbar regions of the spinal cord

Preganglionic neurons in parasympathetic system

emanate from various cranial nerves at the anterior end and sacral regions in the posterior end

Behaviors of the autonomic division

- commands contraction and relaxation of muscles in intestinal and vascular walls (smooth muscle)

- dilate/constrict pupils

- stimulate/inhibit digestion

Sympathetic nervous system

"fight or flight"

Parasympathetic nervous system

"rest and digest"

Cranial nerves

- 12 pairs of nerves numbered by Galen anterior to posterior

- relay information from the brain to regions of the head, neck, and GI track

Cranial nerves that originate from brain stem

III-XII

Cranial nerves that originate from cerebrum

I & II

Cranial nerves in different systems

- some in CNS (I,II,V)

- some have motor component that is CNS and sensory component that is PNS (III,VI,VII)

- others part of PNS

Blastulation

source of ES cells

Major stages of neurodevelopment

1. Neural induction

2. Neural tube formation

3. Regionalization/Patterning

4. Neurogenesis

5. Migration

6. Axonal Pathfinding/Synaptogenesis

7. Target-dependent cell death/Synaptic pruning

Neural induction

- during gastrulation

- forms ectoderm, endoderm, mesoderm

Gastrulation

- days 11-15

- cells of embryo move and form three primary germ layers

Ectoderm

outermost germ layer; produces nervous system and skin

Endoderm

innermost germ layer; develops internal organs

Mesoderm

middle germ layer; develops into muscle and skeleton

- the main neural inducers are made

Main neural inducers

- noggin, chordin, and follistatin (proteins encoded by genes)

- called morphogens

- without, neuroectoderm would become epidermis

- used to help convert ES or iPS stem cells into neurons

Neurulation & Neural tube formation

- days 16-15

- neural tube becomes brain and spinal cord

- neural crest derived as an offshoot of closure of the neural tube

- become sensory and autonomic neurons, neuroendocrine cells, glia, and melanocytes

Regionalization/Patterning

- day 28 and beyond

- Anterior-Posterior (AP) patterning

- Dorsal-Ventral (DV) patterning

Anterior-Posterior patterning

- three primary brain vesicles appear

- boundaries between vesicles are directed by transcription factors, morphogens, and cell signaling genes & molecules

- patterning of hindbrain controlled by retinoic acid (RA) morphogen

The three brain vesicles formed during AP patterning

prosencephalon, mesencephalon, and rhombencephalon

- become forebrain, midbrain, and hindbrain (medulla, brainstem)

Dorsal-Ventral patterning

- notochord releases Sonic Hedgehog (Shh) to initiate the formation of the nervous system

- notochord becomes part of bone and muscle of spinal cord

- floor plate expresses Shh, is secreted as a gradient: high ventral, low dorsal

Sonic Hedgehod (Shh)

- initiates formation of nervous system

- Shh gradient helps set up DV subregions, give rise to either motor neurons or interneurons

- is a "ventralizer"; Ex: induces motor neuron cell fate in spinal cord, monoamine fates in midbrain

- used to induce neurogenesis of ES and iPS cells

Expansion of forebrain (day 36)

- prosencephalon expands and adds telencephalic vesicles

- eye begin to form

- rhombencephalon develops into the metencephalon and myelencephalon

- cranial nerves begin to form

Expansion of forebrain (days 49-90)

- prosencephalon develops into the diencephalon and telencephalon

- telencephalon rapidly develops and covers diencephalon

Expansion of forebrain (6-9 months)

- gyri and sulci form

- cerebellum develops folia

Prosencephalon

forebrain

Mesencephalon

midbrain

Rhombencephalon

hindbrain

Metencephalon

pons and cerebellum

Myelencephalon

medulla

Diencephalon

thalamus and hypothalamus

Telencephalon

cerebral cortex

Differentiation of the telencephalon

- the telencephalic cerebral hemispheres swell and envelop the diencephalon

- optic cup develops, will give rise to retina (only sensory organ in CNS)

Structural features of forebrain

- early development gives general structure of brain

- dorsal telencephalon (called neocortex) is highly expanded in primates and humans

- basal telencephalon includes the basal ganglis

The forebrain functions

seat of perceptions, conscious awareness, cognition, and voluntary action

Thalamus is the gateway to the

cerebral cortex

internal capsule

- Projection of axons from the thalamus are via the internal capsule. If a thumbtack sticks you in the right foot it would be relayed to the left cortex by the left thalamus via the left internal capsule

corpus callosum

the white matter tract that the two hemispheres use to communicate with each other

Cortical neurons

- send axons back to the brainstem through internal capsule

- some project all the way to spinal cord

- project to basal ganglia to control movement

corticospinal tract

cortical neurons that project all the way to the spinal cord for direct control of movement

basal ganglia

includes the striatum in the basal telencephalon and substantia nigra in midbrain

Amygdala

- in the basal telencephalon

- controls fear and emotion

Differentiation of midbrain

- dorsal part becomes the tectum (superior and inferior colliculus)

- ventral part becomes tegmentum (VTA, SNr, etc)

- cerebral aqueduct

Superior colliculus function

visual processing

inferior colliculus function

auditory processing

cerebral aqueduct

connects the third ventricle of diencephalon with fourth ventricle of hindbrain

Differentiation of rostral hindbrain

- dorsal part becomes cerebellum

- ventral part becomes pons (and pontine nuclei)

- pons connects the cerebral cortex with the cerebellum on opposite side using axons called mossy fibers that synapse with cerebellar granule cells

Differentiation of caudal hindbrain

- medullary pyramids carry corticospinal projections heading towards the spinal cord

Neurogenesis sequence

proliferation, migration, differentiation

Neurogenesis

- initially, walls of brain only have ventricular zone (VZ) and marginal zone (MZ)

- radial glia (precursors to neurons & glia) extend a process from ventricular surface to pia.

- some cells start to divide asymmetrically, daughter farthest away from ventricle migrates along a radial glia guide cell to occupy its layer in cortex, never divides again

- most neocortical neurons born between 5th week and 5th month of gestation

Symmetric cell division

generates more precursors than divide

Asymmetrical cell division

generates one post-mitotic cell and one precursor that continues to divide - post-mitotic cell migrates and becomes neuron or glia

Neuroepithelial cells

- initially expand its the precursor pool

- main progenitors of the cerebral cortex during development, produce neurons and glia

Cell fate

driven by differential gene expression during development

- each daughter cell has same genes, some are "turned on" (gene expression)

- factors that regulate gene expression are differentially passed on to daughter cell depending on which plane the cell is cleaved

vertical cleavage

daughter cell has symmetric Notch 1 and Numb expression. Daughter cells remain in VZ to divide again

horizontal cleavage

daughter cell has differential protein expression, notch 1 cell will migrate away, numb cell will remain and continue to proliferate

Notch

- controls the balance between proliferation of neuronal precursor cells and their differentiation into neurons or glia

- Numb may antagonize Notch (controversial)

Factors that affect what a precursor cell will become

- age of precursor cell

- position in ventricular zone

- environment at the time of the last cell division that created it

Development of cortex

- first cells that migrate become subplate

- the next cells form cortical plate, forms from VI down

- assembled "inside out"

- each deeper layer begins to differentiate into pyramidal neurons before the formation of newest layer is complete

- Intermediate zone (IZ) becomes white matter

- ventricular zone, subplate, and marginal zone disappear

"Inside Out" assembly

cells that form each layer migrate past the ones that preceded them

Differentiation

- precursor differentiates once it reaches destination

- dendrite attracted to pia by a guidance module (semaphorin 3A)

Pyramidal neurons

large excitatory neurons- many have long axons that project all the way to spinal cord

Semaphorin 3A

- a guidance module that attracts dendrite to pia (cortical surface)

- high expression in marginal zone

- low expression in lower layers

- repulses axon

- responsible for polarity of pyramidal cell

Final developmental steps

- axon growth and guidance to target - chemoattraction and chemorepulsion

- synaptogensis (formation of synapses)

- target-dependent cell death

- synaptic pruning

- synaptic plasticity

Target-dependent cell death

more neurons are generated than needed

- Target provides a trophic factor that the input neuron needs - nerve growth factor (NGF) or brain derived neurotrophic factor (BDNF)

- mutations in genes responsible for the cell death results in more neurons than normal

Synaptic plasticity

learning & memory, involves molecular mechanisms related to synaptogenesis

Frontal lobe functions

complex human behavior

- prefrontal and primary motor cortex