CNS Physiology Flashcards
spinal cord image
-you can see the individual vertebrae that extend down to L1 and L2 with nerve endings at the bottom
-covered by the meninges and the dura mater has CSF
where do afferent neurons project through?
dorsal horn of the spinal cord
where does the dorsal root ganglian sit?
-a foramen a distance from the spinal cord (intervertebral space)
-cell bodies project through dorsal horn and synapse with interneurons then exit through the ventral roots
what do the ventral nerve roots consist of?
motor neurons
where would you sample from if you want just the motor nerves?
-ventral nerve roots
-usually get torn away when you cut the spinal cord —> need a specific technique to get sample
where would you sample from if you want just the the sensory nerves?
-dorsal nerve roots
-also require a specific technique since you have to go ventrally to keep the ventral motor neurons intact
gyri
outpatchings of the brain
sulci
invaginations of the brain
different views of the brain for pathology
- coronal- patient is facing you
- sagittal- lateral view
- axial- think patient is feet forward so the patient’s right side is on the left side of the picture
what does the CSF do?
-cushions the brain and spinal cord
-supplies nutrients to the brain
-removes waste
-associated with arterial and venous blood supply —> constant turnover between the blood and CSF
how much CSF does the body produce?
-150 mls
-taking 50 mls can help with pressure of CSF and may transiently relieve patients
-drawing 20 mls can be used for diagnostics of MS or lyme since you cannot remove a piece of the spinal cord
-fluid is replaced within an hour
lumbar puncture
-method of sampling CSF
-helps with diagnostics
-emerging role with biomarkers in the CSF
gray matter
regions where the neurons sit
white matter
-axons of the neurons
-tracts are important pathologically
Ex. B12 deficiency selectively involves dorsal and cerebrocentral tracts —> patients will experience symptoms related to abnormalities of white matter tracts
spinal cord
-not just a straight tube
-cervical and lumbar regions, which are enlarged
cervical region
enlarged since this region innervates arms
lumbar region
consists of many motor neurons and is also enlarged since it goes to legs
thoracic region
less pronouncement since it is connected to the ribs and ribcage
cauda cana
-bottom portion of the spinal cord that looks like a horse’s tail
-nerve roots that exit through intervertebral parameter
spinal reflex
-afferent responses through dorsal root ganglion through dorsal horn that either synapse directly onto the motor neuron or the interneuron
-synapse activates muscle and inhibits through interneuron of hamstring so it can relax while the knee extends
-agonist/antagonist muscles are activated/inhibited
major pathways from CNS to PNS
- motor pathways
- sensory pathways
motor pathways
-in the homunculus you can see there are large representations of hands and legs, which is a graphical representation of amount of cortex innervating relevant regions
-hand with large representation along with face and tongue —> allows for fine motor movements
-axons travel through cerebral peduncle —> cross at pyramids —> descend down the corticospinal tract and synapse on motor neurons
sensory pathways
- dorsal column system
- spinothalamic tract
cell types of CNS
neurons, astrocytes, oligodendrocytes, microglia, and endothelial cells
cell types of PNS
schwann cells and muscles
anatomy of a neuron
-dendrites- branches that receive inputs from other cells
-cell body (soma)- contains the cell nucleus
-axon- conducts electrical impulses along the neuron cell
-myelin sheath- insulates the axon to help protect the cell and speed up transmission of electrical signals
-axon terminal- transmits signals
neuronal diversity
-unipolar
-bipolar
-pseudounipolar
-multipolar
Ex. Purkinie cell- anatomically laid out in cerebellum and shows how you have dendritic trees with axons that go deeper into the cerebellum
dendrites
-receive inputs
-consist of several branches that have buds where synapses are formed
-receptors sit on dendrites
soma
-nucleus
-mitochondria
-endoplasmic reticulum
-the typical cell functions
axon
-axon hillock where the soma meets the axon and AP is established —> all the signals are synthesized here
-nodes of ranvier
-myelin sheath to help transmit electrical signals
structural components of axon
-microtubules
-neurofilaments
-measured in blood and CSF –> cut a nerve and you can see these structures
microtubules
-larger, longer polymers with tubular dimers and lots of proteins
-how things like mitochondria are trafficked up and down the axon
neurofilament subtypes
-the light (NFL)
-the medium (NFM)
-the heavy (NFH)
-relevant b/c they can be measured in blood and CSF —> cut a nerve you can see neurofilaments, which can be used as biomarkers
Ex. look at the changes in neurofilaments over time for ALS
axoplasm
cytoplasm of axon with complexity in structure
types of axonal transport
-retrograde
-anterograde
retrograde transport
-slow, backward movement of components like RNA, proteins from distal end to soma using microtubules
-occurs with dynatin and dynein
anterograde transport
-fast, forward-moving
-occurs with kinesin
myelin sheath
-insulation and has lamelle to wrap around axon
-between the regions you have the nodes of ranvier, which allow for rapid transmission
nodes of ranvier
enrichment of Na channels within node and helps move AP down axon
excitability of neuron
-transmit electrical signals down axon
-gather data in dendrite, synthesize in the soma, and transmit via the axon
-dependent on semi-permeable membrane with Na/K pump, Na channels and K channels —> pump brings in K and out Na in 3:2 ratio and keeps cell at resting membrane
action potential
-stimulate the neuron electrically, mechanically, etc.
-Na channels open locally in response to stimulus generating an AP
-Na floods into the cell and AP starts to travel left to right
-as depolarizing current travels down, more Na channels open and you get propagation of AP
-at the same time, upstream Na channels inactivate after only being open for a brief amount of time and K channels start to open and membrane potential is restored
saltatory conductions
-only occurs in regions between myelin sheaths
-regions consist of Na channels
-AP only has to occur with regions between myelin sheath
-helps propagate the AP along axon
EMG/nerve conduction study
average speed of shocking the medial nerve is 49 m/s and in those with guillain-barre syndrome, it decreases from 49 to 21 m/s since the myelin is gone
neurotransmitters
-classical: acetylcholine (NMJ transmission), dopamine (Parkinson’s disorder), serotonin (depression)
-amino acid: glutamate (most neurotransmission in brain is from this), aspartate, GABA (stiff person syndrome- immunity against GAD and prevents the production of GABA), d-serine
-peptides: tachykinin (substance P), opiate (enkephalin), somatostatin, cholecystokinin, vasoactive intestinal peptide
-gaseous: nitric oxide, carbon monoxide
neuronal excitation and inhibition
-tells the difference between light and deep touch
-when Na channels are activated, they produce excitatory postsynaptic potentials (EPSPs)
-when Cl channels are activated, they produce inhibitory postsynaptic potentials (IPSPs)
inhibitory synapse (glycinergic synapse)
released from presynaptic terminal of inhibitory neuron and Cl flows into the postsynaptic membrane
how come we don’t respond to every stimulus?
EPSPs and IPSPs are synthesized and added up
integration
-inhibitory and excitatory signals are summed up anatomically and temporally
-occurs in the neuropil, usually at the initial segments
synaptic potentials
-stimulus from one excitatory input does not reach threshold so no AP fired (APs are all or nothing)
-if neuron fires twice quickly, temporal summation to generate AP
-two excitatory synapses fire together —> generate AP
-inhibitory synapse and excitatory synapse —> no AP generated
what forms the CNS myelin?
-oligodendrocytes
-one oligodendrocyte can myelinate segments of many different axons
-only has one single layer of myelin
astrocytes and health
-things wrong with astrocytes affect disease and health
-help with metabolism of brain and spinal cord
synaptic transmission
presynaptic:
package neurotransmitter —> vesicle fuses to presynaptic membrane —> Ca signals fusion and release of neurotransmitters into synaptic cleft
postsynaptic:
receptors on membrane receive the neurotransmitters
synaptic proteins
more than 1000 proteins function in the presynaptic nerve terminal and over 100 of them function in exocytosis
acetylcholine
neurotransmitter that is the mechanism by which the nerve and muscle are connected
biomarkers for ALS and other neurological disorders
-CSF
-blood/plasma/serum
-brain/spinal cord tissue but difficult to repeat since you can’t go back in for more samples
-urine
-skin has nerve fibers and proteins
-muscles
-electrophysiology
-PET imaging
genetics for ALS
rise in discovery of genes contributing to ALS, which can be made into models
induced pluripotent stem cells (IPSCs)
-yamanaka discovered that you could take mature cells and reprogram them to be immature
-he then discovered that he could reprogram the mature cells to become pluripotent stem cells, which are immature cells that are able to develop into all types of cells in the body
PNS
-cranial nerves exit from brain and brainstem
-divided into somatic (muscles) and autonomic
what do the dorsal root nerves consist of?
sensory neurons
what happens once nerves emerge from the dorsal and ventral roots?
once they emerge, they are mixed nerves with sensory and motor fibers
normal pressure hydrocephalis
buildup of CSF pressures —> perform high volume tap to provide transient relief
dorsal column system
involved with fine touch and proprioception, which helps you know where you are in space
Ex. B12 deficiency patients sometimes have a hard time walking and not b/c they are weak but they are unable to sense their legs —> tell them to look down and they are able to walk
spinothalamic tract
pain and temperature
two types of myelin sheath
-oligodendrocytes in the CNS
-schwann cells in the PNS
dendritic spine
-regions within dendrites where synapses are formed
-there has been research on these and how their morphology changes
Ex. LTP is a remodeling of neurons to form memories and promotes the growth of new spines
what are some functions of astrocytes?
-@ synaptic sites, they are sucking up excess neurotransmitters like glutamate
-releasing neurotransmitters
-things that go wrong with astrocytes can affect synapses
neuromuscular junction
-acetylcholine (A) is released from the motor neurons
-A binds to A receptors —> NA channels open and the muscle depolarizes
-AP opens the T tubules and SR with stores of Ca that is released
-as Ca binds, there is conformational change to allow actin filaments to bind to myosin
-overall: acetylcholine interacts with the membrane of muscle resulting in Ca release to allow for muscle contractions
sensory pathways
-receptors can be mechanoreceptors, tactile fibers around hair, Pacini’s corpuscle
-they transmit all different sensory responses
-sensory neurons can become refractory (desensitized)
-different axon types come in different modalities
if there is phenotypic heterogeneity in neurological diseases, are all mechanisms of ND similar?
-some patients with ALS have speech and swallowing as first symptoms while others have weaknesses
-all mechanisms of neurodegeneration are similar
what can we do with IPSCs?
-record from them electrophysiologically
-mix and match them- take astrocytes from ALS and mix with normal motor neurons
-induce cell stressors
-drug screening
what amino acid is involved in an inhibitory synapse?
glycine
what amino acid is involved in an excitatory synapse?
glutamate
