Neuro Flashcards
Contrast the embryological development of the neural cells and ventricular system.
Neural cells come from the neural tube.
Ventricular system comes from the lumen of the neural tube.
What major adult structures arise from each embryonic subdivison of the neural tube? What is their relationship to the ventricular system?
(L1/2)
Describe the gray and white matter organization of the spinal cord, brainstem, and forebrain.
(L1/2)
Forebrain: Gray matter is on the outside, white matter is on the inside
Brainstem: Is this different?
Spinal cord: Gray matter is on the insider, white matter is on the outside
Contrast grey and white matter.
(L1/2)
Grey matter: cell bodies
White matter: myelenated axons
Contrast the following terms:
nucleus, column, layer/lamina/stratum, tract/fasciculus/lemniscus, funiculus, ganglion, root, ramus, nerve, plexus
(L1/2)
Explain the difference between projection neurons and local interneurons.
(L1/2)
Projection neurons: neurons that have long axonal projections to other regions of the CNS or PNS
Local interneurons: neurons with short projections
How many layers does the cortex have and how does this contribute to its functionality?
(L1/2)
Six layers of cerebral cortex provides a laminar organization within columns to allow for complex processing. There are also varying degrees of thickness depending on the location in the brain leading to different functionality.
Homunculus
(L1/2)
Column of cells that are functionally related by body part. This occurs in both the brain and in the spinal cord.
Describe the general organization of spinal cord and spinal nerves in terms of:
dorsal root ganglia, ventral root ganglia, afferents, efferents, dorsal region (horn), ventral region (horn)
(L1/2)
Contrast: nerve, neuron, nerve fiber, neurites, and neurophils
(L1/2)
Nerve: collection of parallel axons and support cells, a macrostructure with components contributed by many cells
Neuron: an individual nerve cell
Nerve fiber/axon: signaling component of the neuron and associated supportive sheath
Neurites: any projection of a neuron
Neurophil: collective of dendrites, axons, and support cells wtihin the CNS
What are commissures?
(L1/2)
Connections between two different hemispheres including the anterior commissure, posterior commissure, and the corpus callosum are examples
*What structures are present in the telencephalon/cerebral hemispheres?
(L1/2)
Frontal, parietal, occipital, and temporal lobes, insula, amygdala, hippocampus, basal ganglia, corpus callosum, anterior commissure, posterior commissure, fornix, cingulum, arcuate fasciculus, lateral ventricles
Neocortex
(L1/2)
Cortex responsible for vision and hearing? Is this true?
Association cortex
(L1/2)
Integrates primary motor and sensory cortex
Brodmann Areas
(L1/2)
laminar organization with different areas having different abilities
Lateral/Sylvian Fissure
Divides temporal lobe from the parietal and occipital lobe; deep to this structure is the insula
Calcarine sulcus
divides the visual cortex in the occipital lobe
Insula
(L1/2)
Deep to the lateral fissure, connected to the basal ganglia, (considered part of the neocortex?)
What is the location and function of the cingulum and the arcuate fasciculus?
(L1/2)
Telencephalon
Axon bundles that connect regions within one hemisphere?
What is the function of the fornix?
(L1/2)
Connects the hippocampus with other brain regions
*What structure are found in the diencephalon?
(L1/2)
Thalamus is dorsal region of the diencephalon, anterior to the brain stem, & lateral to the third ventricle
Hypothalamus, third ventricle
Massa intermedia/thalamic adhesion: connecting point between the right and left thalamus; however, NO crossing fibers are present
There is also ventral connection to the pituitary gland via the hypothalamus
Thalamus
(L1/2)
Processes the sensory (except olfactory) and motor influences, regulates consciousness
Mass intermedia/ thalamic adhesion
(L1/2)
Connection between thalamus that touch, but do not have crossing fibers
Reticular nucleus
(L1/2)
regulation of thalamus
Hypothalamus
(L1/2)
Coordinating and integrating endocrine, autonomic, and homeostatic functions
What structures are found in the brainstem?
(L1/2)
Mesencephalon/midbrain, Pons, Medulla
Describe the cranial nerves exit from the brainstem.
I - olfactory n is in the cribiform plate but attaches to the olfactory bulb (dienchaphalon)
II (diencephalon)
III, IV midbrain
V hindbrain
VI, VII, VIII @ junction in pons and medulla
IX, X lateral origin
XI from the spine
XII between olives and pyramids
How are connections made between the brainstem and the cerebral hemispheres?
(L1/2)
cerebral peduncles, with some input from the periphery through the cranial nerves directly, and most other information traveling via the spinal cord
*Describe the location of the cerebellum. How is it connected to the brainstem?
(L1/2)
Above the brainstem with two cortical hemispheres and several deep nuclei. It is connected to the brainstem via cerebella peduncles.
*Contrast the primary motor cortices, primary sensory cortices, association cortices.
(L1/2)
Primary motor cortices
Primary sensory cortices: touch, vision, audition; smell and taste
Association cortices: integration, planning, or interpretation of impulses from primary cortices
What part of the brain is damaged in anoxia, epilepsy, and Alzheimer’s?
(L1/2)
Hippocampus
What part of the brain is damaged in Parkinson’s and Huntington’s Disease?
(L1/2)
Basal ganglia
Describe the tegmentum
(L1/2)
It is continuous through the brainstem. There is a pontine, midbrain, and hindbrain portion. Neuronal processes are held here.
Contrast the superior and inferior colliculi.
(L1/2)
Located on the tectum. Superior is responsible for visual reflexes and inferior is responsible for auditory pathway.
*What is the function of the brain stem?
(L1/2)
Neural pathways/tracts between the cerebrum and spinal cord extend through the brainstem and is the target of most cranial nerves that control movement and sensation in the head and neck region. These cranial nerve cell bodies are prone to vascular accidents.
*What is the function of the cerebellum?
(L1/2)
modulation of motor movement, attention, language
damage can lead to ataxia
*Describe the layers and functions of the meninges.
(L3)
Dura mater: periosteum and meningeal layer between which form the dural sinuses
Arachnoid mater: Composed of cap cells, barrier cells, and trabeculae with a subarachnoid space that contains CSF, roots of cranial and spinal nerves, blood vessels of the CNS, and cisterns
Pia mater: vascularized layer that directly contacts the brain and spinal cord
Contrast the epidural space in the cranium with the spinal cord.
The spinal cord has a real space that is fatty that is ideal for drug delivery (ie. epidurals). The dura in the brain directly adheres to the skull making the epidural space a potential space.
Leptomeninges
Arachnoid mater and pia mater together
*Cisterns
(L3)
subarachnoid space enlarged regions that are reservoirs of CSF
How are the meninges embryologically derived?
(L3)
Neural crest cells and mesoderm
What are the majority of meninges made of?
(L3)
Fibroblasts and EC connective tissue; the more connective tissue the tougher the layer
Compare and contrast bacterial, viral, and fungal meningitis.
(L3)
Present with fever, chills, headache, increased CSF pressure, and cloudy CSF
Bacterial: caused by Streptococcus pneumonia or Neisseria meningitidis; fatal if untreated; early treatment with antibiotics; turbid; 60-90% positive gram stain; <0.4 glucoseCSF serum ratio; WCC >500; 90% PMN
Viral: <25 y/o, supportive treatment; clear; <1000 WCC; higher PMN
Fungal: injection of contaminated substance, not contagious; fibrin web; 100-500 WCC; monocytes
Meningiomas
(L3)
Arise from arachnoid cap cells
Most common form of benign intracranial tumor
Slow growing, benign, surrounded by clear order
Treatment is surgical removal
Hemorrhages
(L3)
Most common cause is trauma
Symptoms: headache, neck stiffness, vomitting, depression of lack of consciousness
Can occur in epidural (middle meningeal), subdural (dural sinuses), or subarachnoid space (cerebral arteries)
Describe the brain’s consumption of oxygen.
(L3)
20% but only 2% of water weight
10 second: loss of consciousness
3-5 minutes: irrepabable or fatal
10-20 minutes under hypothermic conditions
Describe the Circle of Willis.
(L3)
Aneurysms
(L3)
bulging of an artery found at ranching points of vessels
Treatment: clipping of bulging portion
Cerebral Embolism
(L3)
occlusion of cerebral vessel by plaque or bacterial
Arteriovenous Malformation (AVM)
(L3)
Proper connections do not develop between major arteries and veins; they communicate with each other by bypassing the capillaries; these are dynamic and will change and grow and might lead to hemorrage
Treatment: surgical removal
Stroke
(L3)
Hemorragic or ischemic (most common; either thrombosis or embolic)
“FAST”
Facial drooping
Arm weakness
Speech difficulties
Time
*Differentiation for hemorragic is sudden onset
Treatment: TPA within 3 hours
What is the blood supply to the spinal cord?
(L3)
Anterior spinal artery, posterior spinal artery, sulcal artery
Contrast the dural sinuses with other veins in the body.
(L3)
The dural sinuses do not have the collection of other cells surrounding them like other veins. They also lack valves thus do not have one way motion.
Describe the production and function of the CSF.
(L3)
Little protein and WBC, no RBC; higher Cl, Mg, and Na than plasma, dramatically lower proteins and albumin than plasma
Protection, buffereing, filtering, cushioning of the brain, excretion of waster products, transportation of hormones and ions
150 mL with a pressure of 70-180 mmH20 which is a pressure high than the venous sytem ensuring that there is one way transport
400-500 mL of CSF/day
Lumbar puncture
(L3)
Level of L1/L2; cauda equina
Cloudy: bacterial meningitidis (due to neutrophils)
IgG: Mutliple sclerosis
RBC: subarachnoid hemorrhage
Malignant cancer: metastasis of cancer
Choroid Plexus
(L3)
Where CSF is made in the lateral, third, and fourth ventricles. They arise from tufts of specialized ependymal cells and form villi. CSF circulates for 6-8 hours before exiting via subarachnoid granulations/arachnoid villus to the venous system
What is the flow of CSF?
- CSF is made in the choroid plexus in the lateral, third, and fourth ventricle. (NB the two parts of the lateral ventricles do not communicate with each other due to the Septum Pellucidum)
- Interventricular Foramne of Monro
- Cerebral Aqueduct (no choroid plexus, narrow and susceptible to occlusion which can dilate the lateral and 3rd ventricles)
- Foramen of Magendie (medially) and Foramina of Lushka (laterally) and central canal of spinal cord
Hydrocephalus
(L3)
Increased CSF volume and pressure leading to enlargement of the ventricles caused by blockage or a failure of the CSF to be reabsorbed
Congenital
Acquired: (three types)
- Obstructive hydrocephalus: Intraventricular foramen, cerebral acqueduct, or subarachnoid obstruction (at tentorium cerebelli or superior sagittal sinus)
- Normal pressure hydrocephalus: misnomer because CSF pressure is elevated typically in elderly patients who exhibit the diagnostic triad of urinary problems, impaired gait, and dementia
- Communicating Hydrocephalus: CSF flow into the venous system is blocked due to cogenital absence of arachnoid villi or blockage of arachnoid villi (by RBC with hemorrage; by protein due to infection)
Blood brain barrier
(L3)
Tight junctions etween endothelial cells that surround the lumen of brain capillaries. Pericytes assist with blood vessle contstriction. Astrocytes regulate blood flow.
fMRI, change blood flow, change oxygen and glucose levels
Low molecular weight and lipophilic will pass; everything else requires active transport
We have to be careful about the central effects of peripheral drugs (ie antihistamines)
Circumventricular organs
BBB is incomplete in these areas and sense concentration of blood components.
For example, the area postrema detects the presence of noxious substances and induces vomitting.
Describe the ratio of glial cells to neurons in the brain.
(L4)
There are more glial cells than neurons.
Contrast neurons and glia in terms of ability to divide and propagate action potential.
(L4)
Neurons can propagate action potential, but glia cannot. Glia have the ability to divide wheras neurons cannot.
Describe the embryological development of glia cells.
(L4)
Astrocytes and oligodendrocytes <– neuroectoderm
Microglia <– mesoderm
In general what disorders are glia connected to in general?
(L4)
Brain tumors, MS, trauma, neurodegenerative disorders, homeostasis issues
Describe the abundance and structure of astrocytes.
(L4)
20-50% of total brain volume; most abundant and largest form of glia; present in gray and white matter
Star shaped processes; highly branched; can have up to 10^5 synapses
Present in gray and white matter end-feet interact with the BBB and form the intervascular lining membrane
Surround neuron cell bodies, dendrites, and axons
Glia limitans
Tripartite synapse
Bergmann glia
(L4)
cerebellum
Mueller cells
(L4)
retina glia
Interlaminar astrocytes
(L4)
Astrocytes in layer 1 of the cortex with tortuous processes
Protoplasmic astrocytes
(L4)
Thick, highly branched, in layers 2-6 in gray matter
Fibrous astrocytes
(L4)
Long, thin, less branched, in white matter
How can we distinguish histological slides of astrocytes?
(L4)
GFAP and Golgi-staining
Glia limitans
(L4)
a layer of end feet of astrocytes lining the pia mater
Tripartite synapse
(L4)
Presynaptic neuron, post synaptic neuron, astrocyte
Communicates with neurons in a bidirectional manner via chemical transmission
What are the functions of astrocytes?
(L4)
Describe the role of astrocytes in the glutamate-glutamate cycle.
(L4)
- The astrocyte takes up glutamate via the EAAT1/2 channel.
- Glutamine synthase converts glutamate to glutamine.
- Glutamine transfers from the astrocyte to the presynaptic neuron via EAAT3/4.
- Glutaminase converts glutamine to glutamate.
*This can also happen with GABA
What are pathologic conditions associated with astrocytes?
(L4)
Glial scars: result from spinal cord injury
Traumatic brain injury: alteration of homeostasis and astrocytes can infiltrate to control electrolyte and fluid imbalance
Amyotrophic lateral sclerosis (ALS): astrocytes release toxins that can damage motor neurons
Epilepsy: issue with glutamate and K balance
Astrocytomas: most common glial tumors
Glioblastoma multiform: most deadly
Descirbe the structure and function of Oligodendrocytes.
(L4)
Found in white and grey matter, smaller than astrocytes with fewer branches; one can wrap around multiple axons; high lipid:protein 80:20; Nodes of Ranvier (saltatory conduction; rich in Na channels)
Form myelin sheath in white matter allowing faster propagation; in gray matter perineural oligodendrocyte with unknown function
How can oligodendrocytes and Schwann cells be identified on histology?
MBP
How are oligodendrocytes involved in pathology?
(L4)
MS: demylenating disease because of degenration of oligodendrocytes; idiopathic
PML: rare fatal disease due to JVC in the white matter in the brain
Infarct, infection, infants have low myeline
Clinical depression
Oligodendriomas: slow growing tumors
Describe the general structure and distribution of microglia.
(L4)
Smallest of all the glia cells; 20% of brain; grey and white matter; immune cells
Id: Iba1 and OX-42/CD11b
Contrast the function of the resting state, active state, and ambedoid microglia.
(L4)
Resting state: rod-shaped bodies, symmetrical processes, inactive
Activation: thicker processes, larger cell bodies, secrete cytokines, chemokines, and anti-inflammatory factors
Ameboid: phagocytosis
Contrast M1 and M2 active microglia.
(L4)
M1: proinflammatory, IL1B, TNFalpha (inflammatory)
M2: arginase I, IL-10 (antiinflammatory), clearance of debris and reduce inflammation via phagocytosis
What is the function of the microglia?
(L4)
Immune cells
- Resident immune cells of brain quickly activate to respond to damage to the brain via phagocytosis
- Mediate inflammatory response in CNS
- Important for CNS development and synaptic plasticity
- Communicate with microglia and astrocytes
What is the histology distinguishing feature of microglia?
(L4)
Iba1 and OX-42/CD11b
What is the embryological development of the microglia?
(L4)
yolk-sac cell
Describe pathology associated with microglia.
(L4)
- Excess TNF alpha and IL1 beta become toxic to surrounding cells.
- These also can exacerbate bacterial meningitis because they promotoe permeability of BBB.
- Microglia targeted in HIV in inflammatory state
- Neurodegenerative disease, Parkinson’s and Alzheimer’s
- MS, autism, environmental toxins
NG2 Cells
Most abundant progenitor cell of any glia; develop into oligodendrocytes, astrocytes, neurons
Satellite Cells
(L4)
Connected via gap junctions, these are a combination between astrocytes and microglia in the PNS.
- Surround the cell bodies of autonomic and sensory ganglia
- Maintain homeostasis by regulating external environment
- Respond to injury and produce proinflammatory molecules
Where are Schwann’s cells derived from?
(L4)
Neural crest cells
Contrast Schwann cells with oligodendrocytes.
(L4)
Schwann cells: PNS, only myelenates one neuron, Schmidt-Lanterman clefts, covered in basal lamina
Oligodendrocyte: CNS, myelenates multiple neuron
Schmidt-Lanterman clefts
(L4)
in Schwann cells, small pockets of cytoplasm
Functions of Schwann Cells
(L4)
- Encapuslate neurons in gray matter w/o myelenating them
- Phagocytose axons that are damaged
- Guide regernation of neurons
- Produce neurotrophins that aid the survival of neurons
- Myelenation of axons
Guillan-Barre Syndrome
Acute inflammatory demyelinating polyneuropathy that causes inflammation of meylin leading to blocked conduction and muscle paralysis. This is triggered by an acute infection and is usually autoimmune. This usually impacts the Schwann cells. It usually begins in the lower limbs and progresses to the face.
Schwannomas
(L4)
Cancers of Schwann cells, capsulated and easily removed
Charcot-Marie-Tooth disease (CMT)
(L4)
Most common inherited neurological disorder; autosomal dominant; weakness in lower leg and foot; severity is highly variable with onset in adolescents; abnoraml myelin sheath structure
Contrast glia cells and neurons.
(L5)
Glia cells can divide and undifferentiated; neurons cannot divide and are differentiated
Describe the structure of the neuron.
(L5)
Dendrites, soma/body, axon
Dynamic cytoskeleton
Plasma membrane is continuous throughout the cell
Contrast the abundance of organelles in the soma and the axon.
(L5)
Soma: RER, SER, ribosomes, nucleus, mitochondria
Axon: No RER or ribosomes
What are the three components of the neuronal cytoskeleton?
(L5)
Microtubules, neurofilaments, microfilaments
Microtubules
(L5)
Alpha&beta tublin –> protofilament x 13 – microtubule
Maintain neuronal processes such as axons and dendrites and they are dynamic via tau.
Describe the role of tau in regulating microtubule.
(L5)
Tau is a protein that stabilizes the microtubule. When tau is phosphorylated tau proteins will dissociate and the microtubules will be destabalized and depolymerized. Altering these kinase/phosphatase activities can impact tau and thus microtubules. (Alzheimer’s and Diffuse Lewey Body Dimentia due to hyperphosphorylation)
Neurofilaments
(L5)
Abundant on the axon and also present in dendrites
Monomer filaments x 2 –> coiled-coil dimer –> tetramer (protofilament) –> protofibril –> neurofilament
Microfilaments
(L5)
Actin monomers important for motility of the growth cone
Dendrites
(L5)
Not myelinated, highly branched
Apical or basal
Neuromuscular spindles or free nerve endings
primary –> secondary –> tertiary dendrites (impact strength of signal; closer will be stronger)
Microtubulues and neurofilaments
mitochondira, ER, polyribosomes (protein synthesis)
Dendritic spines
(L5)
Present on glutamate dendrites but not on all dendrites; thicker shape more mature near cell membrane
Soma/body
(L5)
Large nucleus, RER (protein synthesis), SER (lipid synthesis), golgi apparatuses (modification and packaging), polyribosomes, continuous plasma membrane, mitochondria (energy), nucleolus also large
(RER stained with Nissl, will be blue)
Axon
(L5)
Large amount of microtubules and neurofilaments (“rail road tracks”) that are important for the transport of proteins, vesicles, and organelles. Do not contain ribosomes/RER, but they do have SER and mitochondria. (Not colored blue on Nissl-stain) Generally one axon per neuron, but it can vary in length. Terminal arbors are the terminal branches capped with bouton. Smallest axons will not be myelenated.
Nodes of Ranvier
(L5)
Na/K channels present to allow for saltatory conduction
Axon hillock
(L5)
“gateway” to the axon and determines whether an AP is carried down the axon. If an AP is generated it begins an initial segment (AIS).
Axonal transport
(L5)
Bidirectional along the axonal microtubules.
Anterograde: proteins made in the soma move down the the axon; maintains the structure of the synapse; kinesin is in fast anterograde transport of vesicles and mitochondria; slow as well (unknown mechanism)
Retrograde: materials taken up from the synpase travels towards the soma; dynein is motor protein for fast retrograde transport of growth factors from the synapse; clinically relevant because viruses can travel up retrograde into the brain (ie. encephalitis)
Contrast the types of neurons based on their anatomy
(L5)
Pseudounipolar: bifurcated axonal process, mainly in spinal ganglia
Bipolar: special sensory
Multipolar: multiple dendrites, most neurons in CNS
Amacrine: retinal neurons, no true axon
What are the functional, discharge pattern, and molecular classification of neurons.
(L5)
Functional: sensory, motor, interneurons (local)
Discharge pattern: tonic, fast spiking, phasic
Molecular: excitatory, inhibitory, modulatory, NT it makes
Describe the vulnerability of neurons.
(L5)
- Post-mitotic cells (stem cells in sub-ventricular zone/olfactory bulb and sub-granular zone/hippocampus)
- High energy demands (oxygen 20%, CO 15%, glucose)
- very complex nervous system
- Limited repair mechanisms within the brian
- Variety of insults (self-imposed, environmental toxins, bodily changes)
Criterea for NT
(L6)
- synthesized in neuron
- W/in presynatpic terminal at a concentration that will elicit an effect
- Released in response to presynaptic depolarization (action potential) and Ca
- Specific receptors on postsynaptic cell
- Exogenous administration will have same effect
- Specific mechanism to terminate action of NT
What is the key for most pharmacological regulation of NTs?
(L6)
Recognizing the rate-limiting step
What are the methods of inactivating a NT to end the signalling?
(L6)
Diffusion, enzymatic degredation, re-uptake
How can you classify NT by chemical categories and functional divisions?
(L6)
Chemical: amino acids, biogenic amines, large molcule/peptides
Functionally: neural signaling (amino acids), trans-system modulators (biogenic amines), within system modulators (neuropeptides)
Acetylcholine
(L6)
Autonomic ganglia, PS postganglionic, NMJ, CNS (basal forebrain and brain stem nuclei to the cerebral cortex, hippocampus, and thalamus)
ChAT (enzyme) is in cholinergic neurons and is synthesized in soma and transported down the axon.
Rate limiting: reuptake of choline into presynaptic neuron
What impact will and increase of ChAT have?
(L6)
Increase: increase in ACh production as long as choline is available
What will be the consequence of nerve gas, insectisides or drugs on AChE.
Block AChE which will break down ACh and will have a stronger postysynaptic signal.
Catecholamines
(L6)
Dopamine, NE, and E
Tyrosine hydroxylase is the rate limiting step
AADC/dopa decarboxylase is found in all catecholamines and this step occurs in the cytoplasm
How can we distinguish between dopamine, NE, and E neurons?
(L6)
Based on which enzymes are present.
NE: DBH (synthesized in the cell body and transported down the axon into vesicles so that when NE is released so is DBH; the transport of DBH takes time)
E: DBH & PNMT
The specificity in blocking Dopamine v. NE v E comes from the blocking of the receptor.
Contrast the removal of DA, NE, and E.
(L6)
Reuptake or enzymatic degredation
MAO: DA/NE, requires uptake, presynatpic cell
COMT: DA/NE/E; no reuptake required on postynaptic cell
Where are dopamine neurons?
(L6)
Nigrostriatal system (substantia nigra to striatum): undergoes damage with Parkinson’s disease
Mesolimbocoritcol system (ventral tegmental nucleus to nucleus acumbens and cortex): drug reward pathways
Arcuate nucleus of hypothalamus project to pituitary
Describe the projections of NE in the CNS.
(L6)
Starts in the locus coeruelus and projects to the whole brain and implicated in mood, emotion, and pain.
Serotonin (5-HT)/5-hydroxytryptamine 5-HT
(L6)
Regulator of mood, emotion, behavior, sleep
Rate limiting step: first reaction, impacted by dietary tryptophan
AADC = second enzyme
Reuptake and degredation by MAO
SSRI targets reuptake of serotonin
Cocaine inhibits reuptake of 5HT and NE and DA acting as psychostimulant
Raphe nuclie of brain stem and projects to almost every part of the brain
Histamine
(L6)
Histidine –> Histamine (histidine decarboxylase)
Both the supply of histidine and enzyme are part of the rate limitign
CNS - tubomamillary body of hypothalamus projects to the cortex
no reuptake; enzyme degredation is the primary mechanism
What is the major NT in the CNS?
(L&)
Amino acids
Excitatory: glutamate, aspartate, glutamate, cysteate
Inhibitory: GABA, glycine, taurine, B-alanine
Glutamate
(L7)
Glutamine can either be produced by Krebs cycle in neuron or recylced in glial cell
Packaged into vesicles
Reuptake is both glial cell and neuron
Elevated glutamate leads to epilepsy, anxiety, addiction, ischemic brain damage
Important for neural plasticity and development, learning and memory
GABA
(L7)
major inhibitory neuron of CNS, trace amounts in PNS
Rate limiting step: decarboxylation of glutamate by glutamin acid decarboxylase (GAD)
GAD is only found in inhibitory neurons in CNS
Drugs that enhance GABA: barbituates, alcohol, anaesthetics, benzodiazepines
Drugs that diminish GABA causes seizures, picrotoxin for example
GABA can only be metabolized in glial cells and neurons if alpha-ketoglutarate is present to recieve the amino group which will degrade GABA but make glutamate at the same time
Glycine
(L7)
Major inhibitory NT of the CNS, restricted to the interneurons of the spinal cord and brain stem
Serine –> glycine (serine transhydroxy-methylase)
Reuptake in glial and neural cells
Strychnine targets glycine receptors, convulsions and respiratory arrest
Neuropeptides
(L7)
Synthesis: multi step process with the prepropeptide made in the soma RER, made into active peptide via golgi, and travel in vesciles down axon
Stimulus: Peptides are in larger granules farther from synapse and require a larger stimulus for release
Function: within system modulatros, project locally except for the opiod circuit from the arcuate nucleus to the periaqueductal gray, important pain pathway
Degredation: no reuptake mechanisms for peptides and can only be removed by enzymatic breakdown; thus, it will take longer to replenish these
General functions of receptors
(L7)
NT bind with high specificity
Excitatory/inhibitory (Na/Cl)
Kinetics determine how log channel is open
One NT can activate multiple receptor subtypes - metabotropic, ionotropic, or both
Presynaptic rectpors can autoregulate transmittter synthesis and release
Ionotropic receptors
Ligand gated channel, fast, 4 transmembrane domain, both terminals are extracellular (for example, glycin and serotonin)
Nicotinic ACh receptor
5 subunits with four transmembrane domains that vary and determine permeability to Ca
Permeable to Na, sometimes Ca
Two alpha subunits, bind 2 Ach molecules
GABAa receptor
(L7)
Inhibitory synaptic transmission in brain
Permeable to Cl
Heterogeneous mixing of subunit types
2 molecules of GABA must bind
Allosteric modification: anxiolytics, ethanol, anesthetics, barbituarates make it more effective
Picrotoxin blocks the flow of Cl
Glutamate receptors
only three transmembrane domains and incomplete pore loop, carboxy terminal is internal
AMPA
NMDA
Kainate
AMPA receptors
(L7)
fast activation, permeable to Na/K but NOT Ca; desensitize quickly
NMDA receptors
(L7)
Permeable to Ca, slower kinetics, Na and K a permeable
Voltage dependent, require 2Mg blockade to be removed, glycine agonist
AMPA and NMDA coexist, AMPA provides the voltage needed for Mg to dissociate
Ca is important for memory, learning
Disruption –> neurotoxicity, stroke, and CNS injury
Metabotropic Receptors
(L7)
Slower than ionotropic, either excitatory or inhibitory, longer lasting, 7 transmembrane proteins
G proteins (GTP swaps for GDP), G proteins will activate ion channels or secondary messenger systems, GTPase will cleave GTP to GDP turning it off
Contrast the B-adrenergic receptor and a2 receptors.
(L7)
B-adrenergic: G proteins increase intracellular cAMP
a2 receptors: inhibitory G proteins and decrease intracellular cAMP
Contrast the active zone and the puncta adherentia.
(L8)
Active zone: NT secreted and absorbed
Puncta adherentia: adherent proteins hold the synapse together
What are the characteristics of a synaptic vesicles?
(L8)
small, store non-neural peptide NT, recycled, regulated by calcium, conduct fast spatially precise signaling
Contrast: readily releasable pool, recycling pool, reserve pool
(L8)
Readily releasable pool: docked to cell membrane and released with AP, small easily exhausted, readily released
Recycling pool: proximal to cell membrane, larger, moderate stimulation, longer to exhaust
Reserve pool: majority of synaptic vesicles, intense stimulation when two previous pools are exhausted
SNAREs
(L8)
Calcium-sensitive proteins that mediate exocytosis
Tetanus: disrupts inhibitory GABA or glycine neurons
Botulinum: treat spastic muscles, chronic migrains, tone down wrinkles by disruption SNARES in Ach NMJ
Large dense core vesicles
(L8)
Not part of noraml NT release containing neuroactive peptides, growth factors, hormones, or amines
Neuromodulatory to reshape synapses in a more broad way than normal NTs
Triggered by a train of AP, not a single AP
Synthesized in the cell body in axon terminal, not recyled
Fewer than synaptic vesicles
Clathrin Coated Pits and Vesicles
(L8)
Help with the reuptake of NTs following strong stimulation
How does dopamine function as a neuromodulator? (L8)
Modulated by dopaine via G protein receptors and internal calcium stores in SER and trigger NTs and can act as a neuromodulator
Presynaptic dense grid
(L8)
area of proteins associated with the active zone to define to are of NT release
Postsynaptic Density
(L8)
Proteins immediately next to the synaptic cleft on the postsynaptic side, protein scaffolds around receptor-signaling microdomains
Reduced in neurogenerative diseases
Describe the presence of mitochondria in the presynaptic and postsynaptic part of the cell.
(L7)
Presynaptic - mitochondria for reuptake/release mechanisms
Postsynaptic - no mitochondria
Describe how many glutamate synapses synapse onto dendritic spines.
(L8)
90%
Contrast the different types of dendrites.
(L8)
Plasticity spines: smaller spines that can grow when stimulated
Memory spines: mushrooms, larger, actively in use, associated with memories
Memory is tied to growing and building new dendrites
Abnormal dendrites tied to neural system disorder
Axodendritic synapses
(L8)
synapses on dendritic spines that are generally excitatory
Axosomatic synapse
(L8)
Cell body targets and are generally inhibitory
Axo-axonic Synapse
(L8)
Inhibitory, presynaptic inhibition
Gray Type I Synapses
(L8)
Glutamatergic, excitatory synapses, usually on dendritic spine but can synapse on spine
Gray Type II Synpases
(L8)
Inhibitory, GABA, usually on body
Na/K pump
2 K in and 3 Na out to maintain negative potential inside cells
EPSP
(L8)
Excitatory influx of positive ions, generally caused by glutamate
IPSP
(L8)
Negative ions enter, Cl, prevent AP in postsynpatic cell
How can DA and NE act as neuromodulators?
DA and NE can impact the release of internal calcium modulating the strength of neural chemical signals
Contrast spatial summation and temporal summation.
(L8)
Spatial: Multiple APs at the same time leading to firing of AP
Temporal: Multiple APs in sequence that prevents the neuron from repolarizing making it easier for the AP to fire
What impacts long-term memory?
(L8)
Largely due to postsynaptic changes, increased dendritic spines, increasing connections, insertion of more AMPA glutamate receptors (not NMDA)
How are more AMPA receptors added to contribute to long term memory?
(L8)
- Lots of glutamate stimulation
- Calcium and calcium dependent proteins in the postsynaptic dendrite spine
- Actin polymerization - increase size of spine
- Protein synthesis
- More AMPA inserted into membrane
Describe the role of dendritic spines with autism and Alzheimers.
(L8)
Leading cause of autism is thin immature dendrites
Alzheimers leads to reduction in dendritic spines
Electrical synapses
(L8)
Unlike chemical synapses, these are bidirectional flow of electrical current. Faster and weaker signalling. Gap junctions via connexin. These are important for synchronizing acitivity with learning.
Denticulate ligaments
(L10)
extensions of pia mater that connect to the dura mater to stabilize the spinal cord
Anterior (ventral) median fissure
(L10)
Separates the dorsal and ventral horns of the spinal cord so that they do not communicate.
Dorsal root ganglion (DRG)
(L10)
contains all the cell bodies of the periphery sensory nerves; pseudounipolar; they do not synpase here
Describe the blood supply of the spinal cord.
(L10)
Anterior spinal vessel supplies the anterior 2/3 of spinal cord and all the grey matter.
Posterior spinal vessels supply the posterior 1/3 of the spinal cord and travel medial to the dorsal rootlets.
Posterolateral sulcus
(L10)
Where the spinal dorsal roots enter the spinal cord
Posterior intermediate sulcus
(L10)
Present at T6 and above only dividing the fasciculus cuneatues (upper body) and fasciculus gracilus (lower body)
Anterior white commissure
(L10)
Allows crosstalk to both sides of the commissure and contralateral limbs
Where does the shift between oligodendrocytes and Schwann cells occur?
(L10)
The dorsal root
What are the spinal segments?
(L10)
31 segments:
8 cervical
12 thoracic
5 lumbar
5 sacral
1 coccygeal
Dermatome
(L10)
Area of skin supplied by a single dorsal root
There is no C1 because of the trigeminal nerve
Spinal tap
(L10)
Adult noramlly ends at L2 (L3/4)
Child ends at L3 (L4/5)
Describe the exiting of the spinal nerves in reference to the vertebra.
(L10)
C1-7 exit above the vertebra.
C8 and below exit below the vertebra.
Sulcus limitans
(L10)
Divide the ventral (basal plate) and dorsal (alar plate)
Contrast the intermediolateral cell column (IMCC) and the intermediomedial cell colum.
(L10)
Intermediolateral cell column: in lateral horn, T1-L3, preganglionic SS neurons
Intermediomedial cell column: in lateral horn between S2 and S4, preganglionic PS
Contrast UMN and LMN
(L10)
UMN: originate in cortex & brain stem, do not synapse on target neuron
LMN: synapse on target neurons
Contrast alpha and gamma motor neurons
(L10)
Alpha: Extrafusal (muscle)
Gamma: intrafusal (muscle spindles)
How do MN get input?
(L10)
1) afferent from muscle spindles
2) UMN
3) Spinal cord interneurons (inhibitory and excitatory)
Motor unit
(L10)
Alpha motor neuron and all muscle fibers it innervates
Contrast large and small motor units.
(L10)
Small are for finer movements. Large are for higher force.
Motor neuron pool
(L10)
Motor neurons that innervate one muscle
What type of neuron are the majority of neurons in gray matter?
(L10)
interneurons
Renshaw cell
(L10)
These are a type of inhibitory interneuron in the spinal cord that fire stimulated by the firing of a MN to release glycine. This acts on the MN to prevent tetanus. Targeted by Clostridium tetani.
Describe the organization of grey matter in the spinal cord.
(L10)
Lissaur’s tract: ?
Substantia gelatinosa: poorly myelinated
Nucleus proprius: sensory nucleus
Clarke’s nucleus: sensory, thoracic region, unconscious proprioception
Intermediolateral cell column: SS (T1-L2)
Intermediomedial cell column: PNS (S2-4)
Motor neurons in ventral horn
What types of neuronsn are in the DRG?
pseudounipolar with both central and peripheral processes/axons
What are the nerve endings that innervate receptors in skin?
(L11)
Free endings (pain and temperature)
Merkel’s disk (pressure and texture)
Meissner’s corpuscles (light touch)
Pacinian corpuscles (vibration and pressure)
Rufini’s endings (stretch and slippage)
What fibers carry proprioception, touch, and pressure?
(L11)
Aß fibers, group I, and group II
What are the afferent neurons associated with skin v. muscle?
Skin: Aß, Að, C
Muscles: Group Ia, Ib, II
Group Ia and Ib fibers
Afferents of muscle spindles that carry proprioception from skeletal muscle
Largest diameter, fastest, heaviest myelination
Group II
(L11)
From muscle, fast, but less so than Group I, also heavily myelinated
Aß fibers
(L11)
myenlinated and innervate encapsulated skin mechanoreceptors
Pressure, proprioception, touch, two-point discrimination (varies throughout life)
Contrast the myelination, speed, and diameter of the various afferents.
(L11)
What fibers sense temperature and pain?
(L11)
Að and C fibers from the skin
Að fibers
(L11)
Temperature and pain on the skin, slow and have a little myelin
C fibers
(L11)
Sense pain and itch are slow because of their lack of myelin
Describe free nerve endings in terms of location, function, rate of adaptation, threshold of activation, fibers.
(L11)
Skin
Pain, temperature, crude touch
Slow
High
Að and C fibers
*Highest threshold! Slowest to adapt!
Contrast the receptor type, location, function, rate of adaptation, and threshold of activation of:
free nerve endings, Meissner’s corpuscles, Pacinian corpuscles, Merkel’s disks, Ruffini’s corpuscles, Muscle spindles, Golgi tendon organs, joint receptors
Describe the role of Ia fibers.
(L11)
Primary afferents that wrap around the intrafusal muscle fibers connected by annulospiral endings. Carry information about dynamic stretching of muscle and stop when position is maintained.
Group II fibers
(L11)
Secondary afferents that have flower spray endings on the intrafusal muscle. As stretching increases, so does the firing. are these also dynamic?
Why is the coactivation of the gamma MN important?
(L11)
These will coactivate with the alpha MN with the stretch reflex. These innervation the intrafusal spindle fibers and control the length of the extrafusals. This maintains the tautness of the intrafusal spindles allowing for continuous feedback regarding the length of the muscle. Allows for efficient operation at any muscle length.
Knee jerk reflex
(L11)
Stretch reflex
Patellar ligament stretch –> quads elongate –> Ia and II afferents fire –> alpha MN fire –> quad contracts –> leg kicks
coactivatio of gamma neuron
At the same time, inhibitory neuron fires on the hamstring alpha motor neuron
Explain the stretch reflex when someone hands you a beer :)
(L11)
Passive stretch of bicep –> Ia afferent fires –> alpha motor neuron –> contract bicep
interneurons inhibit triceps
Gamma MN maintain tautness
Flexion (withdrawal) reflex
(L11)
step on pin –> Að fire –> interneurons –> alpha motor neurons –> flexion of muscle
NOT MONOSYNATPIC!
Crossed extensor reflex
(L11)
Inteneurons cross the anterior white commissure to excite contralateral extensor and inhibit the contralateral flexor to extend the opposite leg
Golgi Tendon Organ (GTO)
(L11)
Arranged in series with muscle fibers. Ib afferents wrap around collagen fibers. Sensitive to increase in muscle tension from contraction/shortening. This is a negative feedback mechanism decreasing muscle activation when very large forces are generated. This operates through an interneuron.
Intersegmental reflex
(L11)
Uses the propriospinal pathway/fasiculis proprius are important for pattern generation
Dorsal column lemniscal system (DCML)
(L11)
Carries touch (Aß fibers), pressure (Aß fibers) and conscious proprioception (group I and II)
Anterolateral System (ALS)/Spinothalamic system
(L11)
Pain and temperature (Að and C afferents)
Spinocerebellar
(L11)
Non-conscious proprioception (walking, standing)
Contrast the location in the spinal cord of more mylenated afferent fibers with less myelenated fibers.
(L11)
More myelinated (Aß, I, II) - medial, DCML
lightly myelinated, unmyleniated: lateral (Að, C) - ALS
