Term Test 1 (Lec 1-8) Flashcards
Neuroanatomy
study of the anatomy and organization of the CNS of animals
Radial Symmetry
the nervous system is a distributed network of cells (no brain)
Bilateral Symmetry
have segregated, defined nervous system
standard anatomical position
for humans, is standing with arms at side and palms facing forward (thumbs out)
3 Planes
frontal plane –> (coronal plane) separates the front from the back always anterior and posterior
sagittal plane –> parallel to the sagittal suture (longitudinal plane), Medial & Lateral
transverse plane –> (a cross-section) separates the head from the feet, Superior & Inferior
Anterior/Posterior (front/back)
→ “ante” - before, belly in humans
Medial/Lateral (inside/outside)
→ “medius” - middle, and “lateralis”, to the side
Superior/Inferior (top/bottom)
→ “superior” - above, head in humans
→ “inferior” - below, feet in human
Dorsal/Ventral aka superior/inferior (top/bottom)
→ “dorsal” - from Latin “dorsum”, back, thick dorsal fin
→ “ventral” - from Latin “venter”, belly
Rostral/Caudal aka anterior/posterior (front/back)
→ “rostral” - from Latin “rostrum”, beak or nose, sometimes referred to as cranial
→ “caudal” - from latin “cauda”, tail
What does the central nervous system consists of?
- brain and spinal cord
- white matter (myelinated cells)
- gray matter (cell bodies and dendrites)
Cells of the nervous system
Neurons:
- Convey info through electrical and chemical signals
- Oldest & longest cells
- Functional unit of behaviour
- Limited ability to be replaced
Glia:
- Provide a support system for the neurons
- Variety of types & functions
- Presence is crucial for neurons
→ info only flows from in one direction (under normal conditions)
Parts that make up the Neuron
Dendrites –> short, branched processes, spines, the major site of reception
Cell body/soma –> metabolic center of the cell
Axon –> single, thin, cylindrical process, conduction of electrical signals and action potential propagation
Axon terminals –> branched end of axon in close proximity to dendrites of other neurons, neurotransmission
Types of Neurons
→ neurons are polarized, regardless of the type of neuron, signalling occurs in an organized, consistent manner
→ can be classified based on structure:
- (dendrites branch off axon); unipolar, pseudo-unipolar, bipolar
- (dendrites branch off cell body); multipolar
Remember Figure
Sensory
either directly sensitive to various stimuli or receive direct connections from nonneuronal receptors ~20 million sensory fibres
Motor
end directly on muscles, glands or other neurons in PNS ganglia, maybe a few million fibres
Interneurons
all processes confined within a single small area of the CNS
Projection Neurons
long axons connecting different areas, such as the spinal cord & cerebrum
→ interneurons & projection neurons make up 99% of ALL our neurons
Visualization of Neurons: Golgi Staining
- Silver staining technique for use under light microscopy
- Potassium dichromate & silver nitrate
NeuN → marker of post-miotic neurons
MAP2 → microtubules
Neurofilament markers
Synaptophysin → synaptic vesicle protein (presynaptic)
PSD95 → postsynaptic marker
Visualization of Neurons; Immunohistochemistry
- Localization of proteins (antigen) using antibodies to specific proteins
Examples:
–> NeuN, MAP2, synaptophysin, PSD95 specific for neurons
–> GFAP (Glial fibrillary acidic protein) for astrocytes
Visualization of Neurons: Neuron filling/tracers
- Via injection or axonal transport
Ex: biotin derivatives, GFP, lucifer yellow, Viruses (pseudo-rabies/herpes), etc. - Targeted filling of neurons of interest
- Take advantage of polarity & transport mechanisms within the cell
- Methods for loading; Microinjection, Whole-cell patch clamping, Electroporation
- Often used in combination with a technique like electrophysiology → inject tracer into neuron using the recording electrode
Types of Glial Cells
- “Glia” → greek for glue
- Function to support neurons
- Are not electrically excitable
5 major cell types:
PNS: Schwann cells, oligodendrocytes
CNS: astroglia, microglia, ependymal cells
Schwann Cells
- Principle glial cell of the PNS
- Metabolic support
- Wrap around individual axons to form myelin sheath (electrical insulation)
- PNS axon regeneration
- Unmyelinated PNS axons (small diameter) embedded in schwann cells → slower conductance
Oligodendrocytes
- Myelinating cells of the CNS
- Multiple processes allow one oligodendrocyte to surround multiple axons
- Last cell type to be developed from neural stem precursors
- Larger axons have thicker myelin and longer internodes
- Myelination occurs in the 3rd trimester, and continues into adolescence
Astrocytes
- Most abundant glial cell in CNS (75%)
- Mechanical support of neurons
- Metabolic support (glycogen)
- Regulation of extracellular fluid (K+, neurotransmitters)
- Contact with CNS blood vessels
- Reactive astrocytes following injury/insult
Microglia (10-15%)
- Smallest glia cells
- Overall brain maintenance
- The major role in CNS is to respond to injury
- Healthy CNS → survey for damage/disease
- Activation by inflammation
–> Activated microglia non-phagocytic → begin retraction of processes, also thicken
–>Transformation to macrophage (phagocytic) → take on an ameboid shape, travel to site of injury - Ramified or resting microglia → long branching processes
Ependymal Cells
- Line the ventricle system of the brain and the central canal of the spinal cord
- Ciliated to aid the movement of CSF
- Specialized ependyma produces CSF → choroid plexus
- Regenerative?
Glioma
- ~30% of all brain & CNS tumours
- Astrocytomas, ependymomas, oligodendrogliomas
–> Glioblastoma (Grade IV) → 15% of brain tumours - signs/symptoms dependent on region(s) affected
–> Headache, vomiting, seizures, personality changes, cranial nerve disorders, vision loss, pain, weakness or numbness in extremities - Low survival rates and length
3 properties of Ion Channels
- Ion specific
- open/close in response to certain stimuli
- passive movement of ions down electrochemical gradients across membrane
Types of Ion channels
Ligand-gated –> open in response to binding of ligand (neurotransmitter)
Voltage-gated –> open & close in response to changes in membrane potential (voltage)
Mechanical/stretch gated
Resting Membrane Potential (RMP)
- A semipermeable membrane is electrically polarized
- RMP ranges from -70 to -90 mV
- Extracellular fluid is considered to be 0 mV
- Energy is stored in ionic concentration gradients
Ionic Equilibrium and Resting Membrane Potential (RMP)
All cells have ionic equilibria responsible for their RMP, but only nerve and muscle cells are “excitable”
How is RMP established?
- semi-permeable , selective membrane (for K+ and Cl-), impermeable to Na+
- K+ equilibrates based on electro-chemical gradient (Ek)
- RMP of most cells ~ -70mV
Na+/K+ ATPase (‘pump’)
- Active transport that hydrolyzes ATP to ADP
- 2 K+ into the cell, 3 Na+ out of cell
- Ion flow (current) during action potential disrupts ionic equilibria, therefore pump restores electronegativity
- Water follows sodium! During action potentials, cells swell → pump removes water by pumping out sodium
- Na+/K+ ATPase pump restores gradient (over long-term ONLY) → only required following sustained activity
- Concentration gradients are maintained by membrane proteins that pump ions
Action Potentials (AP)
- Rapid changes in membrane potential of axon
- Propagation begins at the axon of the hillock and continues over long distances, utilizing voltage-gated ion channels
–> 4 important properties: 1) threshold, 2) all-or-none event, 3) conduction without decay, 4) AP is followed by a refractory period
The Axon Hillock &Threshold
- Summation of excitatory (EPSPs) and inhibitory (IPSPs) postsynaptic potentials from presynaptic neurons
–> Temporal (over time)
–> Spatial (over space) - At the threshold voltage-gated Na+ channels open
- High concentration of voltage-gated (Vg) Na+ channels
- Once the threshold is met, Vg Na+ opens to begin AP
- ALL OR NONE → if the threshold is met, an AP will always fire
The Action Potential (Visual Graph)
Refactory Periods
Absolute refractory period:
- Cells cannot respond to further stimulation & the inactivation of Na+ channels
Relative refractory period:
- Cells can respond, but requires a greater-than-normal excitation
→ refractory periods ensure APs only generate/propagate in one direction
Action Potential Propagation
The Synapse
- The specialized junction that allows neurons to communicate w/ one another, as well as target organs
- Elements of the synapse: Presynaptic ending, synaptic cleft, postsynaptic element (distinguished by the presence of a swarm of NT-filled synaptic vesicles
- Types: chemical or electrical
Steps in Synaptic Transmission
- Production of neurotransmitters
- Packing of neurotransmitters
- Release of neurotransmitters
- Binding to receptors
- Termination of neurotransmitter action
Synthesis of Neurotransmitters (NTs)
- Main types: small amines, amino acid, or (neuro) peptides
- Small molecule NTs are synthesized in the axon terminal by enzymes
–> Ex. acetylcholine (choline acetyl-transferase; ChAT) - Peptide NTs are synthesized in the cell body and transported to the presynaptic endings
–> Often synthesized as a larger precursor peptide
–> Ex. corticotrophin-releasing factor (CRF)
Packing of Neurotransmitters
- Most NTs are packaged into synaptic vesicles
–> Highly concentrated, protection from degradation
Small vesicles:
- 40nm in diameter
- Contain small molecular transmitters
- Located near the presynaptic membrane
Large vesicles:
- >100nm in diameter
- Contain neuropeptide transmitters & sometimes small molecule transmitter
Release of Neurotransmitters
- Ca2+ -mediated secretion
- Depolarization of presynaptic terminal opens voltage-gated Ca2+ channels
- Synaptic vesicles fuse with the membrane (exocytosis)
Binding to Receptors
Small vesicle NTs: diffuse rapidly across the synaptic cleft, rapid binding to the receptor
Large vesicles Nts: slower release, more distance receptors, overall slower response
- Effects of NTs are determined by the receptor(s) in the postsynaptic membrane
Responses can be:
- Fast or slow
- Excitatory (EPSP) or Inhibitory (IPSP) → depends on the channel (Na/K/Cl) activated
Rapid Synaptic Transmission
- Example: Acetylcholine at nicotinic receptors
- NT binds to a ligand-gated ion channel (ionotropic)
- Alters permeability of the postsynaptic membrane by opening or closing the channel
- The selectivity of the ion channel determines the postsynaptic effects
Slow Synaptic Transmission
- Example: Acetylcholine at muscarinic receptors
- NT binds to G-protein coupled receptor (metabotropic)
- The binding of NT causes the release of G-protein subunit which leads to altered concentrations of second messengers (prolonged effect)
- 2nd messenger binds to the ion channel to alter the permeability
Termination of Neurotransmitter Action
- NTs need to be removed quickly so that the postsynaptic membrane can prepare for subsequent release of NT
Mechanisms:
- Reuptake by the presynaptic membrane or neighbouring glial cells
–> Ex. serotonin, norepinephrine, dopamine
- Enzymatic inactivation
–> Ex. acetylcholinesterase (AChE)
- Uptake by postsynaptic terminal
- Diffusion out of the synaptic cleft
The Electrical Synapse - “Gap Junctions”
- Electrically coupled to one another that allows the passage of ions and other small molecules
- Made up of numerous Connexons
- Direct spread of current from one neuron/cell to another
Advantages:
- No delay in transmitting electrical info
- Useful for neurons that need to fire synchronously (ie. respiration)
- No need to synthesize vesicles or NTs
Disadvantages:
- Loss of functional individuality – one cell’s depolarization results in ALL cells depolarization. Ie. loss of “control” (myocardium = heart)
Embryology - Germ Layers
Endoderm : gut, liver, lungs
Mesoderm: skeleton, muscle, kidney, heart
Ectoderm: skin & nervous system
Primary Neurulation
- 3rd - 4th week of development
- Notochord (mesoderm) induces overlaying ectoderm to differentiate into neuroectoderm
Neurulation:
- Induction of ectoderm to differentiate by mesoderm
- Development of the neural tube, running the length of the embryo
- A flat neural plate begins to fold forming paired neural folds
- Folds fuse together beginning in the neck area & continues in both directions to form the neural tube
- Cells on the edge of the neural plate for neural crest cells (PNS)
Cells of the Nervous System (Figure)
Errors in Neurulation: Spina Bifida
- Incomplete closure of caudal end of neural tube
- Range in the severity of the defect
- Occulta
–> 5% of the population
–> Incomplete closure of vertebrae - Meningocele
- Myelomeningocele
–> Most severe
–> Spinal cord & meninges in sac-like cavity on the back
Errors in Neurulation: Encephalocele
Sac-like protrusion of the brain & surrounding membranes
Errors in Neurulation: Anencephaly
- Incomplete closure of the rostral end of the neural tube
- Lack of telencephalon (cerebrum)
The Early Neural Tube
Ventricular zone:
- Neural progenitor cells
- Neuroblasts & glioblasts
Intermediate/mantle zone:
- Accumulation of neurons & glial
cells
- Gray matter
Marginal zone:
- Cell poor
- Neuronal & glia processes
- White matter
Spinal cord Development
- Sulcus limitans separates the sensory & motor of the spinal cord
- Dorsal portion → alar plate (sensory)
- Ventral portion → basal plate (motor)
Spinal cord Development (CAUDAL neural tube)
- Motor neuron from the basal plate sends projections to the muscle
- Dorsal root ganglion (DRG) sends projections both centrally (CNS) and peripherally (PNS)
Spinal Cord Development Summary (Figure)
Brain Development: Secondary vesicles by GW6
- Telencephalon → grows much more rapidly than other regions
- Diencephalon
- Mesencephalon
- Metencephalon
- Myelencephalon
At 3 primary vesicles:
- telencephalon/diencephalon = forebrain
- mesencephalon = midbrain
- metencephalon/myelencephalon = hindbrain
At 5 secondary vesicles:
- telencephalon = cerebral hemisphere/lateral ventricles
- diencephalon = thalamus hypothalamus/third ventricle
- mesencephalon = midbrain/cerebral aqueduct
- metencephalon = pons, cerebellum/upper portion of fourth ventricle
- myelencephalon = medulla oblongata/lower portion of fourth ventricle
Brain development (cont.)
- Telencephalon grows at a greater rate than other vesicles
- C-shaped arc growth around insula
- Primary sulci form GW14-26
Figure to Know!
Neuronal Migration
- Most neurons produced in VZ migrate radially (red)
–> Somal translocation
–> Guided by radial glial cells - Early neurons → somal translocation → extension of basal process
- Later neurons → radial glia guides
- Tangential migration (blue)
–> Medial & lateral ganglionic eminence
–> Inhibitory cortical interneurons
Neural Crest Cells - PNS development
- Develop from the cells on the lateral aspect of the neural plate
- Highly proliferative
- Differentiate into a number of neural and non-neural tissues
- Migrate throughout the embryo
Two types: cranial & trunk
Differentiation of Neural Crest Cells (Figure)
Neurocristopathies
a diverse class of pathologies involving abnormal cells derived from the neural crest
PNS Repair/Regeneration
- Neurons lost to disease/injury generally not replaced
- Axon transection
–> Wallerian degeneration
–> Schwann cell proliferation
–> Increased RNA synthesis in neuron - If innervation successful, function is restored
What is the Cephalic Flexure?
separation of the hindbrain and the forebrain
(MUST KNOW TO LABEL FIGURE)
Major CNS Divisions (Figures)
Hemisphere Connectivity
- 2 major connective tracts between hemispheres
Corpus Callosum: Interconnects most cortical areas
Anterior commissure: The connection between temporal lobe cortical regions
Sulci
- 4 major sulci
- Names of other sucli are derived from their location within cerebral lobes/location to major sulci
Lateral surface: Central sulcus (of Rolando); Lateral sulcus (sylvian fissure)
Medial surface: Parirtooccipital sulcus → separates parietal and occipital lobes; Cingulate sulcus
(MIST KNOW HOW TO LABEL FIGURE)
Gyri
- Gyri are named in relation to the sulci they are beside
- Correspond to functional areas
Examples;
Precentral gyrus vs. postcentral gyrus
Superior, middle & inferior frontal gyrus
Lobes of the Cerebrum (Figure)
Functional Anatomy of the Cerebrum
Frontal lobe:
- Motor functions → precentral gyrus (purple) contain primary motor cortex (starts all movement)
- Broca’s area → production of written & spoken language
Parietal lobe:
- Somatosensory info → postcentral gyrus (green) contains primary somatosensory cortex (touch, temp, pain)
Occipital lobe:
- Vision → contains primary visual (pink) & association cortices
Temporal lobe:
- Superior temporal gyrus (blue) → primary auditory cortex
- Wernicke’s area → comprehension of language
The Limbic Lobe (System)
- Role in emotional response & memory
- telencephalon/cerebral structures
–> Cingulate gyrus & parahippocampal gyrus
–> Hippocampus
–> Amygdala - Diencephalon structures
–> Thalamus
–> Hypothalamus
Internal Cerebral Anatomy
- Limbic system nuclei
–> Amygdala (Am)
–> Hippocampus (HC) - Basal Ganglia
–> Globus pallidus (GP)
–> Caudate ©
–> Putamen (P) - Diencephalon
–> Thalamus (Th)
–> Hypothalamus (H)
Basal Ganglia & Internal Capsule
- Roles in eye movement, motivation & working memory
Internal capsule:
- fibres interconnecting cerebral cortex to thalamus (anterior limb IC, Putamen, genu IC, globus pallidus, posterior limb IC) & basal ganglia → determine yes or no if a movement is performed → permission
- Caudate nucleus + lentiform nucleus → basal ganglia
Brainstem
- Midbrain
- Hindbrain
- Pons → projection of brain stem
- Medulla
- Attachment point for most cranial nerves
–> Cranial nerve reflexes - Long tract functions
- Ascending reticular activating system
–> Consciousness → dogs & cats cannot inhibit
–> Dreaming activates RAS
–> Low RAS activity = deep sleeper
Cerebellum
- Longitudinal divisions
–> Vermis
–> Cerebellar hemispheres - 3 lobes
–> Anterior
–> Posterior
–> Flocculonodular (oldest) - Functions
–> Coordination of trunk & limb movements
–> Eye movements
–> Postal movements
–> Vestibular ocular reflex
Meninges of the Brain & Spinal Cord
3 layers:
Dura matter
Arachnoid mater
Pia mater
- Provide mechanical support of the CNS
- Cerebrospinal fluid (CSF) filled subarachnoid space
Dura Mater
- thick, tough, callagenous membrane
- Fused with the endosteum (iiner periosteum) of the skull → goes into central sulcus and under cerebellum and spinal cord
- Adheres to underlying arachnoid
Dural septa (folds):
- Falx cerebri → into central sulcus
- Tentorium cerebelli → between cerebellum and spinal cord
- With few exceptions, spaces do not exist on either side of the dural membrane
Two potential spaces:
Epidural: between cranium and outer dural surface
Subdural: within innermost dural layer, near arachnoid boarder
- Dura mater contains venous sinuses that drain the brain
–> Superior sagittal sinus
–> Left and right transverse sinuses
–> Straight sinus
Arachnoid Mater
- A thin, avascular membrane in direct contact with dura mater
Arachnoid trabecula: small strands of collagenous connective tissue within subarachnoid space
- Give arachnoid mater its spider web-like appearance
Arachnoid villi: small protrusion through the dura
mater into venous sinuses
- Reabsorption of CSF into the venous system
Subarachnoid Cisterns
Large pockets of subarachnoid space filled with CSF
Major cisterns (4); interpenduncular, poutine, quadrigeminal, and cisterna magna
Pia Mater
- “Tender” mater
- Thin, connective tissue layer in direct contact with surface of CNS → touching brain on ventral aspect
- Contact with arachnoid trabecula on other side
- Cerebral arteries & veins surrounded by pia before entering/exiting the brain
–> Perivascular space
Meninges & the Spinal Cord
- Same meninges as those surrounding the brain with a few important differences → continuous
1. Vertebral cana contains an epidural space between periosteum & dura
- Pia mater gives rise to longitudinal denticulate ligaments → spinal cord anchor → support for spinal cord from moving in the vertical column → anchors in tailbone
- Lumbar cistern at caudal end of spinal cord
Ventricular System Embryology (Figure)
Ventricular System
- Lateral Ventricles (2)
–> Paired, C-shaped structures
–> 5 parts (frontal, occipital & temporal horns, body & atrium - Interventricular Foramen
- Third ventricle
–> Boarded by thalamus & hypothalamus - Aqueduct (of Sylvius)
- Fourth Ventricles
–> Located in the hindbrain
–> “Space” between the cerebellum and the pons & medulla
–> Communication with subarachnoid space via 3 apertures (recess)
CSF Ventricular Flow (Figure)
“Drainage” of CSF back into circulation (Figure)
Choroid Plexus produces CSF
- Lines lateral ventricles, pass through IV-foramen, & roof of 3rd ventricle
- Separate stand in 4th ventricle
- Component of blood-brain barrier
- Specialized area where ependymal cells & pia mater are in direct contact
Choroid Plexus
- Specialized ependymal cells → choroid epithelium → Apical surface tight junctions
- The increased surface area through folding → total surface area > 200 cm2
Hydrocephalus
- “Water on the brain”
- CSF is constantly produced = Excess CSF production
- Blockage of circulation
- Deficient CSF reabsorption
- Enlargement of the ventricle
- Compression of brain tissue
Symptoms: headache, vomiting, nausea, papilledema, sleepiness, coma
Infants: bulging of the cranium
Treatments: placement of a shunt
Arterial Blood Supply
Internal carotid arteries (ICA):
- Branch of common carotid arteries
- Bifurcates into middle and anterior cerebral arteries (MCA & ACA)
- Blood supply for most of the cerebrum
Vertebral arteries:
- Branch of subclavian arteries
- Fuse at pontomedullary junction to form basilar artery
- Branches form posterior cerebral artery (PCA) & multiple cerebellar arteries
- Blood supply for brainstem, parts of cerebrum & spinal cord
Circle of Willis
ACA: Anterior Cerebral Artery
MCA: Middle Cerebral Artery
ICA: Internal Carotid Artery
PCA: Posterior Cerebral Artery
- Connection between internal carotid and vertebral-basilar arterial systems
- Posterior communicating artery: ICA to PCA
- Anterior communicating artery: connects ACA branches
Functions of the Circle of Willis
- Normally, little blood is moved along anterior and posterior communicating arteries
- If one major vessel either within or proximal to the circle of Willis becomes occluded, the communicating arteries allow for perfusion of distal tissue
- Most effective when occlusion occurs slowly over time
Cerebral Arteries – Medial Surface
Anterior cerebral artery (ACA):
- Medial surface of frontal & parietal cortices, corpus callosum
Posterior cerebral artery (PCA):
- Temporal cortex & some occipital cortex
Cerebral Arteries – Lateral Surface
Middle Cerebral Artery (MCA):
- 60-80% of blood flow from internal carotid artery (ICA)
Upper division: Frontal & parietal
Lower division: Temporal & occipital cortices
Blood Supply to Hindbrain (Figure)
Venous Return
2 sets of veins drain in the brain:
Superficial veins:
- Lie on surface of cerebral hemispheres
- Drain to superior sagittal sinus
Deep veins:
- Drain structures in the walls of the ventricles
- Converge on internal cerebral veins
- Drainage to straight sinus
Venous Drainage
- Sagittal & straight sinus drain into transvers sinuses
- Transverse sinus → sigmoid sinus → internal jugular vein
- Vascular problems involving veins less common than arterial problems
Aneurysms
- ballon-like swellings of the arterial walls
- Most often formed at or near arterial branch points
Consequences:
Compression of brain tissue
Rupture → subarachnoid hemorrhage
Blood Brain Barrier (BBB) (Figure)
Circumventricular Organs (CVOs)
- Locations where the cerebral capillaries are fenestrated & allow for relatively free communication
- Located around 3rd and 4th ventricles
Sensory organs:
- Area postrema: monitors blood for toxins, induces vommiting
- Vascular organ of the lamina terminalis (OVLT): regulation of fluid balance
- Subfornical organ
Secretory organs:
- Median eminence of hypothalamus & posterior pituitary: neuroendocrine role
- Pineal gland: secretion of melatonin
