Introduction/Basic Physiology Flashcards
What is the helpful pneumonic for thinking through the differential diagnosis of neuropathology?
- VITAMIN C
- Vascular
- Infectious
- Traumatic
- Age-related/degenerative
- Metabolic/nutritional/toxic
- Inflammatory
- Neoplastic
- congenital
What are the 4 foundational cases for understanding the role of the brain and nervous system?
- 1848 - Phineas gage - importance of frontal lobe for behavioral inhibitions
- 1861 - Paul Broca’s patient - stroke in a specific area of the brain causing an inability to form language, combine with other patients and see that that area is the language center
- 1953 - H.M. - removal of temporal lobe sections bilaterally, or part of hippocampus, and no short term memory, or permanent anterograde amnesia
- 1999 - transient, reversible depression from Deep Brain Stimulation
What are brodmann’s areas?
- Cytoarchitectonic variation in the cerebral cortex
- An accepted way of organizing the architecture of the brain into functional domains
- 52 total areas now based off of similarities on cellular and tissue level
- Oversimplified, but still used
Where, in relation to the central sulcus, do the primary motor and somatosensory cortices lie?
- Primary motor cortex VENTRAL to central sulcus
* Primary somatosensory cortex DORSAL to central sulcus
What are the given examples for behavioral therapies?
- Psychotherapy
- Counseling
- Biofeedback
What are the given examples for physical therapies?
- Surgery
- Exercise
- Spinal manipulation
- Electroconvulsive therapy
- accupuncture
What are the given examples for pharmacotherapies?
- Perscription medications
- Non-prescritpion drug use
- Herbal remedies
- Diet/nutritional therapies
The end goal of therapy for neuropathology is what?
• It all overlaps, produce lasting changes in behavior, lasting functional changes in the circuitry of the nervous system that underlie the behavior
What are the given elements of the neurologic exam?
- Mental status exam/psychiatric exam
- Reflex exam
- Sensory exam
- Motor exam
- Cranial nerve exam
- Examination of coordination and gait
What are the given elements for determining neuropathologies?
• The pneumonic - VITAMIN C
What are the given elements of the neuroanatomical localization?
- Generalized vs. localized
- Muscle
- NMJ
- Peripheral nerve
- Spinal cord
- Brainstem
- Subcortical (Basal ganglia, cerebellum)
- Cortical (vascular problems?)
What are the questions used while determining neuroanatomical localization?
- Can the symptoms be explained by an identifiable pathologic change?
- Can you account for symptoms with a process affecting the NS generally, or can a single focal/multifocal process explain the pattern?
- If focal can explain symptoms, is it at muscle? NMJ? Peripheral? Spinal cord? Brainstem? Cortical? Subcortical?
- Does the problem line up with a vascular problem?
What is meant by commissure?
In Neurology - A bundle of nerve fibers passing from one side in the brain or spinal cord to the other. - connecting one side of the brain to another as well
* a commissure is neuronal connection between symmetrical sides of the CNS (brain or SC)
The fissure of Roland refers to what structure?
- Central sulcus
* Separates the frontal and parietal lobes
The Sylvian Fissure refers to what structure?
- Lateral sulcus
* Separates the temporal lobe from the frontal and parietal lobes
How many “layers” of the cortex are there?
• 6, and they have to do with cell body layers histologically from superficial (I) to deep (VI)
What is meant by somatotopy?
• Topographic association of positional relationships of the body to functional areas of the cerebral cortex
What is meant by homunculus?
- The figure of a human, projected with a “scale” to the area of the cortex dedicated to it
- Projected on the brain surface
What is a decussation?
- A place in the CNS where fibers from contralateral sides of the brain cross each other
- Depicted in the brain stem
- Looks like a roman numeral X or 10
What important concept did Cajal help define in 1906?
- Neuron doctrine, neurons are the discrete functional units of information processing
- They were surrounded by glia, a more support role cell
What important discovery did Kandel elucidate?
• The “epigenetic” component of memory and learning
Neuronal stimulation leads to longer term changes like gene regulation (CREB)
What important concept did Hebb postulate in 1949?
- Synaptic plasticity - building and removing connections in the brain
- Neurons that fire together wire together, and thus the cellular basis of learning
- Hebb’s rule: if cell A fires a lot under a certain stimulus, it’s connections with cell B will grow stronger (more pronounced with neurons firing concurrently)
What important concept did Sherrington elucidate in the 1930’s?
- That neurons functioned by electrochemical mechanisms
* Electricity will result in a chemical release which in turn affect electrical current
What direction is the information flowing in the dendrite? The axon?
- From dentrite to soma, from soma through axon
* Dentrite is afferent, axon is efferent
How many ventricles in the brain?
- 4, two lateral and then III and IV
- The lateral ventricles feed into the midline III ventricle which goes into the IV ventricle, the farthest back in the neural tube
- Lateral ventricles are in the cerebral cortex
- The C shape of the lateral ventricles is a big clue to the folding of the neural tube
- The forebrain portion of the neural tube bends down and “under” to make the C shape
What does CSF look like and where is it produced?
- CSF is normally clear, made by choroid plexus, a specialized structure within the ventricles
- Specialized secretory tissue sitting within lateral ventricles
- Ventricles hold about 10mL of fluid
- From the IV ventricle CSF goes into the subarachnoid space, surrounding the entire CNS
- You make way more CSF than the whole system can hold
- There are apertures in the IV ventricle that allows for CSF to get into the rest of the system, and if there is any block, there is a buildup of fluid because choroid plexus doesn’t change the production
- The result is hydrocephaly, and the ventricles expand into the neighboring tissues, eventually causing damage to neuronal tissue
What vessels supply blood to the anterior surface of brain vs. posterior portions?
- Posterior = from vertebral artery
- Anterior = from internal carotid
- Very little overlap between the two systems normally
- But very few brains are normal. There are often variations in the patterns of cerebral arterial architecture
What is the cellular basis for fMRI?
- Synaptic activity results in local increases in blood flow
- Due to coupling of glial responses with vessel dilation
- Astrocytes monitor synaptic activity via metabotropic glutamate and ATP receptors
- Increases in extracellular ATP or glutamate (consistent with lots of NT release) will increase intracellular Calcium through IP3 signalling
- Astrocytes respond to increased calcium through releasing metabolites of the COX-1 pathway
- Result is smooth muscle relax and vessel dilation
- Can be blocked by COX inhibition
What are the white matter terms vs. grey matter terms?
• Ie. Peduncles, tracts, nucleus, etc.
Do neurons have direct access to capillaries?
- NOPE. They are surrounded by glial cells
- Thus a CNS drug MUST be highly lipophilic and have a high volume of distribution
- The glial cells and the endothelial cells in BBB are densely packed with selective, active transport mechanisms
How do astrocytes deal with the circulatory system?
- They help establish and maintain the BBB
- Astrocytes surround cerebral blood vessels to regulate blood flow and keep crap from leaking out
- Astrocytes maintain endothelial cell tight junctions
- Endothelial transplant cells will, when astrocytes are present, go from being fenestrated to having tight junctions, showing astrocytes are responsible for that signaling pathway
In PNS, what glial response helps regenerate an axon?
- Need to get better info on this
- Microglia are activated, schwann cells help re-establish connections
- In CNS, the astrocytes inhibit axonal re-growth
What happens to the saturating neurotransmitter in the synapse?
- That’s one of the functions of the astrocytes. They suck up the extra neurotransmitter with high affinity receptors
- Either recycle it back to the axon terminals or it enymatically destroys it
- The neuron terminals themselves have limited re-uptake?
- Astrocytes can modulate the activity of the synapse, and in part because of this re-uptake mechanism/job
Is it the transmitter that determines the valence of a synapse?
- Valence is inhibitory/excitatory.
* NO, the transmitter is received by a receptor that dictates the response
Do microglia only react to local damage?
- No. evidence from mice suggest that microglia will be activated at the brain-termini even from a nerve that has been cut in the periphery
- They are ripping out now-useless terminals from damaged nerves. Don’t waste brain space
- Play a role in the plasticity of the brain
Do microglia come from the same embryonic place as the rest of the nervous system?
• Nope. They do not come from ectoderm
• Think of them as the macrophages of the brain and they arise accordingly from hematopoietic areas
• Migrate into brain before BBB forms
If there is a high concentration of ATP in a tissue, what is that indicative?
• Tissue damage/injury
• Think of the microglia movie where they attacked the ATP leak in the brain
Schwann cells do what?
- Determine axonal regeneration
- In the PNS, not the CNS
- Produce myelin
Oligodendrocyte does what?
- Wraps axons with myelin
- Also called oligodendroglia
- Lays on top of the axon and wraps it with lipid rich myelin
- They live within the CNS. Not PNS. Marks the change
- Essentially form a barrier to axonal regeneration. Thus injury in CNS stays as such
What is chromatolysis?
• Loss of coloring by histologic stain due to the negative feedback loop, think of a motor unit no longer needed because of injury or something
What is retrograde signal?
- Feedback mechanisms from axon terminal that determines continued sending of proteins along cytoskelaton or not
- Like a muscle that is now injured, that neuron innervating the motor unit will have feedback to stop spending so much energy on it
Glial cells in the PNS permit what?
- Regeneration, which doesn’t happen in CNS?
* Yes, there is a glial “barrier” to regeneration in the CNS
Glial cells in the PNS permit what?
- Regeneration, which doesn’t happen in CNS?
* Yes, there is a glial “barrier” to regeneration in the CNS
What are the three main types of glial cells?
• Myelinating glia, microglia, astrocytes
What is axoplasmic flow?
- Transported proteins from soma to periphery
- Protein synthesis is NOT in the axon mostly (very few ribosomes in the axons or dendrites)
- When axons are separated, the peripheral end degenerates while the proximal end, attached to soma, is fine
- Another reason why neuronal regeneration can get a bit weird. Axons grow where they may and the plasticity of the brain re-interprets the new informational architecture
What are Nissl bodies?
- The tons of densely packed ribosomes on the RER
* Neurons make a ton of proteins (big cell, long processes, and tons of cellular transport)
What is a Nissl stain and what does it do?
- Very common neurological histology stain, preferentially stains RNA, helpful for seeing nucleolus of soma
- The nucleus of the soma by comparison are quite clear
What is the axon hillock?
- Specialized (electrically) area as soon as the axon comes off the soma
- Determines whether an action potential will be propagated
What property of water molecules can be harness for a fMRI?
• The fact that water molecules tend to move “down” the tract of axons so you can “map” the direciton of water molecules and thus tracts through the brain
