Neuroscience 1 Flashcards
Gray matter increases with:
learning
What are the steps of a reflex?
- Hammer tap stretches tendon –> stretches sensory receptors in leg extensor muscle
2A. Sensory neuron synapses with and excites motor neuron in spinal cord
2B. Sensory neuron also excites spinal interneuron
2C. Interneuron inhibits motor neuron to flexor muscles
3A. Motor neuron conducts AP to synapses on extensor muscle fibers –> contraction
3B. Flexor muscle relaxes because activity of its motor neurons has been inhibited. - Leg extends
Neurogenesis increases with:
activity
What are the four distinguishing features of advanced nervous systems?
- Cellular specialization
- High storage capacity and adaptability
- Areal specialization (ie lobe)
- Functional cooperation (groups of neurons act together to produce an effect)
What are the 5 types of neuroglia?
- Astrocytes
- Oligodendrocytes
- Microglial cells
- Glial stem cells
- Oligodendrocyte precursor
What are the best predictors of intelligence when comparing brains?
- Foliation
2. Neuronal density
What process defines the midline, anterior-posteriorand dorsal-ventral axes of the embryo?
Gastrulation
What process is central to gastrulation by defining the midline of the embryo and inducing formation of the neural ectoderm?
Notochord formation
What are the neural precursor cells?
Neural ectodermal cells
What is the effect of bone morphogenic protein (BMPs) on ectoderm?
Formation of epidermis, *an example of neural induction
What is BMP and where is it produced?
BMP, bone morphogenic protein, is produced, by mesoderm. It is a subclass of TGFb
What factors inhibit BMP signaling?
Chordin, Noggin, Follistatin etc., produced by the notochord
What happens when BMP is inhibited?
Ectodermal cells take on a neural fate, *example of neural induction
What is the default pathway for neural induction of ectodermal cells?
Neural fate. BMP responsible for transcription factor activation leading to epidermal differentiation
TAKE HOME:
Neural induction requires the coordination of multiple signaling pathways. complexity
Cells that make up the neural tube are:
Neural stem cells
How does the neural tube close?
Both anteriorly and posteriorly, like a zipper
Name two vitamins helpful in preventing neural tube defects.
Folic acid, B vitamins, (cholesterol)
When does the neural crest pinch off? What do these cells become?
The neural crest stem cells pinch off from the neural tube at neural tube closure. These cells go on to become cranial neural crest cells, trunk neural crest cells, cardiac neural crest cells and vagal/sacral neural crest cells.
…in other words, cells in PNS
In dorsal/ventral patterning, the process by which groups of cells become different from one another, ventral signal is secreted:
SHH, (motor)
In dorsal/ventral patterning, dorsal signal is secreted:
TGFb family, mainly BMPs (sensory)
The notochord induces formation of the neural plate and neural groove, but these are also dependent on:
SHH
What is the process by which SHH leads to ventral (motor neuron) cell fates?
- SHH binds to Patched (PTC)
- PTC relieves inhibition of Smoothened (SMO)
- Smoothened activates Gli1 transcription factor family (zinc fingers)
- Gli1 induces transcription to make the cell ventrally fated.
Cyclopia is the result of:
Shh patterning defect
Shh is known to regulate 3 key things in development:
- Polarity
- Proliferation
- Cell differentiation
Disruptions in the Shh pathway can lead to:
- Holoprosencephaly (telencephalon does not bifurcate)
- Cyclopia and misplaced nose (polarity of head issue)
- Medulloblastomas
- Basal cell carcinoma
In addition to BMPs and Shh pathways, what two things play key roles in the development of the dorsal ventral polarity?
RA - retinoic acid (endplate and floorplate) and FGF (near notochord)
What are the results of anterior posterior (A/P) patterning?
Formation of spinal cord Rhombencephalon --metencephalon - future pons --myelencephalon - future medulla Mesencephalon - future midbrain Prosencephalon - --diencephalon - future thalamus and retina --telencephalon - future forebrain
What genes are important in A/P patterning?
Hox genes, involved in defining segmental differences in the spinal cord, medulla and pons, and is major in formation of brain stem and spinal cord
Where is there no Hox code?
Brain (prosencephalon and mesencephalon)
What occurs in OTX2 knockout mice?
OTX2 knockout embryos completely lack forebrain and neural structures
What is the ventricular zone?
Thin strip of cells surrounding the CSF-filled ventricles , where neural stem cells and neural progenitor cells divide and differentiate to give rise to cells in the CNS
What is the difference between a neural stem cell and a neural progenitor cell?
(1) Neural stem cell - Can give rise to any cell type in the nervous system, unlimited potential and self renewal
(2) Progenitor cell - derived from the neural stem cell but have more restricted fate (can be either a glial progenitor cell or a neural progenitor cell)
How does the brain develop in the ventricular zone?
NSC’s divide symmetrically (2 daughter NSCs) until they don’t anymore, and then divide to one NSC and one progenitor. Then finally they will have a symmetrical division into 2 neural progenitors. This happens without growing the size of the ventricular zone, so the expansion is lateral.
Neurogenesis precedes?
Gliogenesis, which starts after the peak of neurogenesis
In order to keep tight tabs on the numbers of NSCs, progenitors, neurons and glia forming, and the timing of their generation, what signaling pathways need to get involved?
- Notch
- bHLH - basic helix loop helix TF (proneural)
These control neural progenitor differentiation and are antagonistic.
Notch signaling requires:
cell to ell contact, through Delta
How does Notch work?
At low to moderate levels of Notch stimulation through Delta, Notch is cleaved and goes to the nucles to activate bHLH TF.
Glial differentiation goes in what order?
- Neurogenesis
- Astrogliogenesis
- Oligogliogenesis
Neurons in most brain areas are all generated by the when in pregnancy:
second trimester
When does the majority of gliogenesis occur?
After birth in humans
What is the inside-out pattern of cortical development?
Radial migration in which first born neurons migrate radially along radial glia to the cortical plate, but each subsequent generation migrates past the previous one.
Hows does inside out cortex form?
Mutation in ECM protein reelin
Developmental disorders implicated in gene migration problems include:
Autism
ADD
ADHD
Schizophrenia
Why can’t interneurons migrate radially as in cortical layer formation?
Because they are coming from the LGE and MGE - laterial and medial ganglionic eminences, therefore they migrate tangentially
Both CNS and PNS are built by:
immigrants
What is a CT scan?
Computed axial tomography
Rotating x-ray beam
Rate of attentuation varies by tissue composition
What are the advantages of CT?
Faster and less expensive than MRI
Can be used as an initial screening tool
What are the disadvantages of CT?
Use of X-ray
Lower spatial resolution than MRI
Less contrast between soft tissues
What is CT used to detect?
infarction tumors calcifications hemmorhage bone trauma
What is an infarct?
Loss of blood supply and thus oxygen to portion of the brain
Why are infarcts more clearly visualized on MRI?
Superior spatial resolution
What is MRI?
Based on principles of nuclear magnetic resonance
What are the advantages of MRI?
No radiation (radio waves instead of x-rays)
High resolution and detailed visualization of soft tissue
Can identify wide range of pathological processes
Functional/chemical imaging
What are the disadvantages of MRI?
Waiting lists
Claustrophobia
Long study duration
What are the physics of MRI?
A spinning proton (like in water) placed within a large, external magnetic field will align with or against the external field. The proton will precess, or wobble, at a frequency proportional to the magnetic field. As we turn the RF pulse off, the PROTONS REALIGN with the external magnetic field. Simultaneously, the ENERGY that each spinning proton absorbed from the RF pulse DECAYS. As the energy decays, an RF signal is emitted.
What is a T2 weighted image?
MRI scanning of tumor: T2 weighted scans utilize a pulse that permits better visualization of lesions.
What is MRS?
Magnetic Resonance Spectroscopy; the permits the study of the chemical structure of the brain; can study: N-acetylaspartate (NAA) Choline (Cho) Creatine (Cr) Lactate (Lac)
Creatine is a:
glial marker
NAA is a:
Neuronal marker
Choline is a marker for:
demyelination
Lactate is found in the brain during:
ischemic events
What is DTI?
DTI measures water diffusion orientations within axons
What are the advantages of fMRI?
Good for studying cognitive tasks, to understand the sites of neural reorganization following stroke or injury
What is PET?
Use of cyclotron to prepare radioactive isotope tracers, injection of tracers, which bind to physiological sites, scanner images the positron-emitting tracer upon its decay.
How has PET been used in management of AD?
Hypometabolism in various brain regions have been associated with severity of clinical symptoms
What is the APOE-4 allele?
Genetic risk factor for AD
Give an example of intraoperative MRI.
Co-localization of MRI and DTI scans allows surgeons to identify way in which the white matter tracts are affected by a tumor.
What is MRI good for identifying?
Neoplasm
Demyelination (MR spec)
Degenerative diseases (Cortical atrophy)
What does MRI look at?
Brain structure
Vasculature
Chemical structure
Fiber tracts
What are the advantages of PET?
Functional imaging
Physiological variables can be determined
What are the disadvantages of PET?
Ionizing radiation
Costly, limited access
Tracer production
What is PET used for?
Psychiatric disorders
Addictive disorders
Epilepsy
What measurements does PET provide?
Perfusion
Metabolism
NT integrity
Neurons that conduct visceral pain are distributed in the
sympathetic nervous system
Neurons that conduct visceral sensory non-pain information are distributed in the
parasymptathetic nervous system
Cell bodies of visceral afferent fibers that conduct visceral pain are located in the ___ along with cell bodies of somatic afferent fibers.
dorsal root ganglia
The visceral afferent fibers of the myocardium are located:
T1-T5
Explain the dermatomal effect of a heart attack.
The cell bodies of somatic afferent fibers that supply the skin of dermatomes of T1-T5 are located in the same dorsal root ganglia as the afferent fibers of the myocardium.
What are the exceptions to dual innervation?
Cutaneous blood vessels
sweat glands
hair shafts
–receive sympathetic input only
Where is myelin found, pre or postganglionic neurons?
Preganglionic neurons
Name the two types of sympathetic ganglia:
- Prevertebral ganglia (5 major prevertebral ganglia)
2. Paravertebral ganglia
Where are preganglionic sympathetic neurons located?
Intermediolateral horn, T1-L2, spinal cord
How does the preganglionic sympathetic neuron exit the spinal cord?
White ramus communicans
Why do gray rami outnumber white rami?
Because there are gray rami for each of the 31 pairs of spinal nerves, and only white rami for the sympathetic neurons
The sympathetic preganglionic neurons in the T1-T4 region of the spinal cord synapse with postganglionic neurons in the:
paravertebral ganglia
In the spinal cord region _____, the sympathetic neurons will target abdomino-pelvic viscera. They will pass through the paravertebral ganglia without synapsing, and travel to synapse on the prevertebral ganglia.
T5-L2
The cranial outflow has four pairs of parasympathetic ganglia:
- Ciliary ganglia
- Pterygopalatine ganglia (CN VII)
- Submandibular ganglia (CN VII)
- Otic ganglia (CN IX)
What is the central control center of the ANS?
Hypothalamus - sensory input related with visceral function, smell, taste, temperature and changes of levels of various substances in the blood
Pain (sensory) impulse processes travel with:
sympathetic fibers
Where are non-pain (sensory) impulse cell bodies located?
Specific nuclei in the brain, processes travel with PS fibers
Where do somatic motor neurons synapse?
In skeletal muscle – no ganglion
The postganglionic fiber (axon) exits the ganglion via a gray ramus communicans to join:
either a dorsal or ventral ramus (branch of spinal nerve) for distribution to the periphery
Where are the paravertebral ganglion?
Thoracic (11-12)
Lumbar (4-5)
What structures are innervated by the superior cervical ganglion?
Skin of the face
Smooth muscles of the eye
Lacrimal and salivary gland
Heart
The middle cervical ganglion and inferior cervical ganglion innervate the:
heart
The T1-T4 paravertebral ganglia innervate:
heart
lungs
smooth muscles of the bronchi
Axons from T5-T9 level form the ______ which synapse in celiac ganglion
greater thoracic splanchnic
Axons from T10-T11 level form the _____ which synapse in the superior mesenteric ganglion and aorticorenal ganglion
lesser thoracic splanchnic nerve
Axons from the _____ level form the LEAST THORACIC SPLANCHNIC NERVE which synapse in the renal ganglion.
T12
Axons from the L1-L2 form the LUMBAR SPLANCHNIC NERVE which synapse in the ________.
Inferior mesenteric ganglion
Postsynaptic axons of CN VII innervate:
Pteropalatine ganglion --lacrimal glands --pharynx --palate Submandibular ganglion --submandibular and sublingual gland
Postsynaptic axons of CN III innervate:
the smooth muscles of the eye
Postsynaptic axons of CN IX innervate:
parotid gland
PS splanchnic nerves synapse with the postganglionic neuron in:
microscopic ganglia close to/on the organ they innervate:
ureters, urinary bladder, repro organs, large intestine
Pelvic splanchnic nerves leave the spinal cord via which root?
anterior –> sacral spinal nerve
The output from the hypothalamus controls the autonomic centers in the:
spinal cord and brainstem
The PNS is anatomically constituted of:
cranial nerves (12 pairs) spinal nerves (31 pairs)
The dorsal horn contains __1__ neurons that receive input from the periphery, which the ventral horn contains __2__ neurons that innervate specific muscles.
- ventral
2. dorsal
Why are there only 30 dermatomes but 31 spinal nerves?
First cervical spinal nerve C1 has no cutaneous terminus
The ventral/anterior root contains axons of:
motor neurons
The dorsal/posterior root contains the processes of:
sensory neurons
What is a plexus?
Network of axons and vantral rami that come together and redistribute differently.
What is a radiculopathy?
Compressed spinal nerve roots
What are the signs and symptoms of radiculopathy?
Sensory loss/deficit in the dermatomal distribution of the affected root
Motor function loss/deficit in the myotomal region of the affected root
What is a myotome?
A group of muscles innervated by the same spinal segment
The dorsal ramus supplies:
motor and sensory
skin, muscles of the back
The ventral ramus supplies:
Ventral and lateral skin and muscles of the trunk
gives rise to the nerves of the limbs
What is a plexopathy?
Nerve injury to entire plexus
What are the small molecule NTs?
- ACh
- Amino acids -glutamate, aspartate, GABA, glycine
- Biogenic amines
- Purines
What are the biogenic amine NTs?
Catecholamines ie norepi, dopamine, epi
Serotonin
Histamine
What kind of GABA receptor is ionotropic?
GABA-A
What kind of GABA receptor is metabotropic?
GABA-B
ACh receptors that are ionotropic are….what is their effect?
nicotinic…excitatory, as in NMJ
What is an antagonist of ACh?
Scopolamine, atropine
What is the effect of sarin gas?
Inhibits acetylcholinesterase
What is an autoimmune disorder of ACh receptors?
Myasthenia gravis
How do you treat MG?
Acetylcholinesterase inhibitors, steroids, thymectomy works in 50% of cases
What are the symptoms of MG?
Ptosis, severe fatigue, diplopia
What is the precursor of glutamate?
Glutamine, which can cross the BBB
What is requird to open an NMDA receptor?
glutamate AND glycine
What are the three ionotropic glutamate receptors found in the CNS?
- NMDA
- AMPA
- kainate
What is excitotoxicity w/r/t glutamate?
High intracellular glutamate is toxic to neurons. Repeated activation of glutamate receptors can excite neurons to death.
What are the ionotropic GABA receptors?
GABA-A and GABA-C
What kind of drugs are benzodiazapines and barbituates?
GABA agonists
What is GABA made from?
Glutamate and pyroxidin phosphate
Where is glycine NT most typically found?
Spinal cord
What is the effect of excess synaptic glycine in the infant?
Lethargy and mental retardation
Are there metabotropic receptors for glycine?
No, ionotropic only
What is the effect of glycine as a NT?
Opens Cl- channels (inhibitory)
What is an antagonist of glycine receptors?
Strychnine
The substantia nigra to the striatum, and the ventraltegmental area (VTA) to the striatum are tracts for what NT?
Dopamine
What is the striatum made up of?
Putamen and caudate nucleus
Antagonists of dopamine receptors in the medulla are used to treat:
Nausea and vomiting
How is dopamine made?
From tyrosine in the nerve terminals
What are the disorders associated with dopamine disregulation?
- Parkinson’s - not enough dopamine
- Schizophrenia - too much dopamine
- Cocaine use - also causes net increase in dopamine in synaptic cleft
How do you treat Parkinson’s?
L-DOPA
Where is norepinephrine found in the brain?
Locus coreleus
How is norepi made?
From dopamine in nerve terminals
What are the metabotropic receptors of noreip?
alpha and beta adrenergic receptors
What is an inhibitor of both dopamine and norepi transporters, causing a et increase of them in the synapse?
Amphetamine
The Raphe nuclei in te upper brainstem, projecting widely into the forebrain, is the location of what NT?
Serotonin
How is serotonin made?
From tryptophan in nerve terminals
What is the majority of serotonin receptors?
Metabotropic majority…these are implicated in psychiatric disorders
Tyrosine –> __1__ –> Dopamine –> __2__ –> Epinephrine
- Dihydroxytryptophan (DOPA)
2. Norepinephrine
What is the rate limiting step in biogenic amine synthesis?
Tyrosine hydroxlase
Tryptophan –> __1__ –> __2__
- 5HT
2. Serotonin
What is the function of MAO inhibitors?
Block breakdown of biogenic amines, used for anti-anxiety and anti-depression
What is the function of tricyclic antidepressants?
Block reuptake of NE and 5HT
What is the location of cell bodies of neurons that transduce smell?
Olfactory epithelium
Olfactory epithelium neurons relay information via axonal projections through the ____ to the olfactory bulb.
Cribiform plate
Bulbar neurons project via the lateral olfactory tract to the piriform (olfactory) cortex located at the tip of the:
temporal lobe
What is contained in the olfactory epithelium?
Basal cells, neurons and supporting cells
What are steps 2 and 3 in signal transduction in olfactory neurons, after the odorant is delivered to the epithelium?
Odorant diffuses to reach cilia
Odorant reacts with receptor protein (binds)
What is the effect of the odorant binding to its receptor?
Causes depolarizing cell potential via G protein cascade
Neurons expressing a particular olfactory receptor have what kind of distribution?
Zonal distribution pattern
How are cells in the olfactory bulb organized?
Like an onion, in concentric layers
What are the layers of the olfactory bulb?
Glomerular layer
External Plexiform layer
Mitral cell layer
Granule cell layer
What are the interneurons of the olfactory bulb?
Periglomerular cells
granule cells
What cells are the relay neurons that project to the olfactory cortex?
Mitral and tufted cells of olfactory bulb
What cells modulate the activity of the mitral and tufted cells?
The inhibitory interneurons: periglomerular and granule cells
What is the outermost layer of neurons of the olfactory bulb?
Periglomerular cells
What is the fundamental unit of organization in the olfactory bulb?
Glomerulus
What is the projection of epithelium in the olfactory bulb goes in what shape?
From quadrant to quadrant
Within a quadrant, the axonal projections bring together the axon terminals of all “like-neurons.” All of the neurons expressing a particular olfactory receptor converge onto the same set of _____
glomeruli
Explain the rule of one OR-one glomerulus.
Olfactory neurons are broadly tunes and all the neurons expressing a single OP synapse together in a single glomerulus.
Olfactory glomeruli are activated by:
odorants
The taste buds of the tongue are innervated by what cranial nerves?
7, 9, 10 (10 to larynx)
The ventral posterior medial nucleus of the thalamus the hypothalamus and the amygdala project to:
the insula, frontal cortex
Gustatory axons innervate:
the nucleus of the solitary tract, which has projections to the ventral posterior medial nucleus of the thalamus
What is the cellular organization of taste buds?
Taste pore - microvilli - taste cells - basal cells - synapse - gustatory afferent axons - receptor cells
How are salt and sour stimuli transduced?
Through ionic transduction mechanism results in an intracellular increase in Ca and transmitter release (Salt - amiloride Na channel and acid - H+ sensitive cation channel)
How are sweet, bitter and umami tastes transduced?
Through GPCR mechanism – increases cAMP – stimulate TRPM5 Ca2+ channel via IP3
Can single axons respond to many different primary stimuli?
Yes, but they have a specific preference for one stimulus over another.
What cranial nerve conveys oral irritation?
Trigeminal nerve
The growth cone is a key decision-making structure of:
axon pathfinding
Lamellapodium looks like ___1___ and is made up of __2__.
- Fan
2. Actin and MTs
F-actin in lamellapodia and filopodia is responsible for:
direction-choosing
Filopodia is made of:
actin (G-actin)
Name 3 examples of non-diffusible attractive axon guidance molecules.
- Collagen
- Fibronectin
- Laminin
Non-diffusible attractive growth cone signals bind to growth cone receptors (integrins) which trigger a signaling cascade favoring:
growth and elongation
CAMs are calcium-
INdependent, cell adhesion molecules
What is the purpose of CAMs?
Modulate the cytoskeleton
L1 CAM is associated with:
Fasiculation, bundling groups of axons as they grow
Cadherins are calcium-
dependent
What are DCC family netrins?
Diffusible attractive signaling molecules, secreted by target cells in midline of embryo
What is the effect of repulsive axon guidance molecules?
Promote actin depolymerization and growth cone collapse
Aggregan, Hyaluronan and Tenascin are examples of:
non-diffusible repulsive molecules
Why is cell movement in the CNS inhibited?
Abundance of hyaluronan, environment favors cell-cell interaction over cell-matrix interaction
The CNS ECM is a major barrier to what:
Brain regeneration in adults
Retina –> V1 –> V2 –> V4 –> Temporal lobe (inferotemporal cortex) is what?
Visual hierarchy where each level is a level of visual information processing, ie orientation tuning, then curvature, contours, then 3D shapes etc.
What is ambylopia?
Lazy eye