Term
| What is the basic structure and development of a cortical sub-circuit? |
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Definition
Neural progenitors grow from ventricular zone to sub plate, via intermediate zone.
Layer VI is first to develop above sub plate and below cortical plate. Order is VI, V, IV, III, II, I.
Layer IV: Thalamic input
Layer II/II: Cortico-cortical and to layer V
Layer V: Project to thalamus, midbrain and brainstem
Layer VI: Project to thalamus |
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Term
| Describe how developing neuroblasts migrate to the cortical plate during cortical development. |
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Definition
Neuroblasts ascend along radial glial cells from ventricular zone to cortical plate (via intermediate zone).
Layer VI is first to be established below cortical plate |
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Term
| What is the role of beta catenin in cortical development? |
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Definition
Signaling molecule and transcription factor expressed by neural progenitor cells that is normally degraded in absence of Wnt signaling.
Beta catenin stabilization stimulates transcriptional cascade that biases the system toward proliferation, rather than differentiation (expands precursor population).
**Stabilization will increase cortical area without expanding cortical thickness** |
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Term
| Describe the role of FGF8 in the development of cortical map structure |
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Definition
| Released from anterior telencephalon and responsible for specifying position of barrel fields (in utero electroporation of FGF8 leads to ectopic posterior expression and will duplicate barrels) |
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Term
| What happens if you put visual inputs into an auditory cortical region? What does this tell us about cortical organization? |
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Definition
If retinal input goes to MGN of thalamus (auditory), visually evoked responses can be found in rewired A1. Orientation maps appear to be present and horizontal connections are more like V1 than A1.
These data suggest that INPUT determines functional identity, rather than precursor identity. |
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Term
| Describe the tonotopic organization of the cochlea |
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Definition
| Basilar membrane is stiff at base (high frequency) and floppy at apex (low frequency). |
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Term
| Describe the basic circuitry of the MNTB:LSO connections |
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Definition
LSO (ILDs) receives glutamatergic excitaion from ipsilateral CN and glycinergic inhibition from contralateral CN via MNTB (CN to MNTB connection is excitatory).
Refinement begins before hearing onset, as evidenced by glutamate uncaging. |
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Term
| Describe the developmental refinement that occurs in the MNTB-MSO circuit. What step requires auditory input? |
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Definition
ITDs
1) Glutamate from Ipsilateral CN
2) Glycine from MNTB and LNTB
Sound is required for transition between both dendritic and somatic MNTB inputs to strictly somatic inputs onto MSO neurons |
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Term
| What is the evidence for experience-dependent plasticity in the development of the Inferior Colliculus and Auditory Cortex? |
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Definition
Click-reared (altered temporal patterning) mice do not develop sharp tonotopic organization (BF responses do not sharpen) in the IC or AC.
If you rear AC with tone-pips, you get maps biased toward to the tone pip frequency. |
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Term
| What is the effect of noise-induced hearing loss on functional map structure in the auditory cortex |
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Definition
| NIHL at high frequencies causes loss of neurons responding to those frequencies in contralateral ear, with expansion of border regions. |
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Term
| How does plasticity in the adult cortex differ from the developing cortex? |
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Definition
| It is slower and requires stronger changes (such as lesion or motivation with dopaminergic modulation). |
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Term
| What are the different classes of early behaviors? |
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Definition
1) Anticipatory: develop with reference to actions that will be useful later (grasp reflex)
2) Adaptive: serve specific functions at particular stages (hatching behavior)
3) Substrative: form basis upon more complex behaviors can be formed (crawling- fine motor skill development) |
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Term
| Describe the timelines of behavioral development in the Drospophila larvae. |
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Definition
1) Localized, isolated contractions occur up until 15d (myogenic) due to muscle activity
2) Unilateral, propagated contractions occur between 17-18d and are dominated by spontaneous neural activity
3) Peristalsis develops at 19d with onset of stimulus-evoked activity.
**If you remove the notochord (mesoderm inducer), all cells become sensory neurons, but you still get neurogenic movements** |
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Term
| True or False: Early motor patterns are generated in the brain and not the spinal chord. |
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Definition
| False! They come from the spinal chord. |
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Term
| Describe the development of the local "bending" circuit in the Leech. What principle of behavioral development does this demonstrate? |
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Definition
1) All connections between neurons begin as excitatory electrical synapses (skin and longitudinal muscles)
2) Some of these synapses are replaced by inhibitory chemical synapses (GABAergic). IF you add bicuculibe, you lose this transition.
**Inhibition enables circumferential contractions, leading to changes in local bending**
3) Circuits are built in stages! First , there are bursting electrical synapses, and then GABAergic chemical inhibition is introduced. |
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Term
| Describe what is meant by "coghill's sequence" of early behavior in the fish. |
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Definition
| Early neck bend is followed by spreading contraction down body line of zebrafish. As excitation spreads, commisural inhibitory interneurons inhibit contraction of contralateral wall musculature (E:I balance). |
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Term
| What is the role of sensory input in the development of early Xenopus swimming? |
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Definition
| Not required! With anesthesia, they still swim normally and ventral root recordings are maintained! |
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Term
| Why is chick hatching an "adaptive behavior" and how does it develop? |
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Definition
1) It serves a specific function at a particular developmental stage, and is therefore "adaptive"
**If you place chicks inside a glass egg, they will attempt to "re-hatch," illustrating the ENVIRONMENT is the trigger**
2) Motor neurons fire in response to sensory stimulation in juvenile stages, but dendritic trees are prune in mature stages, where pro-legs are eliminated. |
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Term
| What are true "instinctive" behaviors? Provide an example. |
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Definition
Those that are activated by environmental signs (Sign stimulus) and follow fixed action patterns (FAPs), which are more complex then reflexes and are preceded by an orienting behavior (FAPs are not tuned by stimulus characteristics, but are ON or OFF)
2) Goose will attempt to return displaced egg to its nest with its neck, even if the egg is removed mid-stream! |
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Term
| What are "central pattern generators"? |
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Definition
Stereotypical behaviors that are present very early in development (without environmental experience or sensory feedback). It is an "instinctual behavior" that develops without sensory input (vs. a FAP that requires a sign stimulus).
Example is Swallowing, where CPG is located in dorsal swallowing group of nucleus solitarious within dorsal medulla oblongata. |
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Term
| What is the role of hox genes in behavioral development? |
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Definition
Regulate the localization and expression of genes required for behavior (define regional specificity).
Remember, the location of genes in the spinal chord determine behavior (wings act like feet if their neurons are switched around).
Deletion of UBX shortens peristaltic movements. |
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Term
| Provide an few example of a behavior that is strongly influenced by sensory feedback. |
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Definition
Opposite of CPGs like swallowing!
Swamp swallow song: cannot produce songs when they are deafened.
There is a "Critical period" when input is required for birds to learn the correct songs. Some birds learn new songs each season! (neurogenesis and new synapse formation each time). |
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Term
| True or False: Many neurons die normally from apoptosis |
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Definition
True
30% of DRG and 70% of cortical! |
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Term
| How does apoptosis differ from necrosis? |
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Definition
Apoptosis is cell-autonomous and protein-synthesis dependent. It occurs without inflammation and involves macrophages engulfment.
- Cells shrink and fragment, cytoskeleton collapses, SPECIFIC inter-nucleosomal cleavage (vs. random DNA in necrosis) occurs and cells bud off apoptotic bodies. |
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Term
| Why might counting the number of apoptotic cells underestimate the true population? What else could you use? |
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Definition
Apoptotic cells are cleared away very quickly!
Use In Situ End Labeling (ISEL) to visualize and count cells with DNA damage in particular regions |
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Term
| How could you determine experimentally if non-mitotic cells are targeted for apoptosis? |
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Definition
| Label with In Situ End Labeling (death) and BRDU (actively dividing cells) and look for overlap. |
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Term
| What is the evidence that supports the notion that neurons die by apoptosis at specific times and locations? |
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Definition
1) Remove limb buds before innervation occurs and you reduce the number of DRG and motor neurons in the spinal chord (target number determines cell survival)
2) Add limb bud prior to innervation, you increase DRG neurons
3) % loss from NM (pre) and NL (post) is bird auditory system is comparable, but rate of death differs (faster in pre-synaptic). Apotosis therefore probably has a pre-synaptic trigger. |
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Term
| Describe the intrinsic pathway of apoptosis. What is the role of inhibitors of apoptosis? |
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Definition
1) Cyt C released from mitochondria activates Apaf1, which coordinates with and activates pro-capspase 9.
2) Complex cleaves and activates executioner caspase 3.
**Inhibitors of apoptosis complex with caspases and inhibit their action, unless IAPs are bound up by pro-apototic factors like DIABLO** |
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Term
| What happens in caspase 3 knock-out mice? |
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Definition
| Cell death still occurs at normal rate in motor, sensory and sympathetic neurons, though morphology of dying cells lack apoptotic markers. This cell death likely involves reactive oxygen species! |
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Term
| How does BCL-2 inhibit apoptosis? |
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Definition
| Inhibits pro-apototic BAX. Both are regulators of apoptosis, while Apaf1 is an adaptor in the intrinsic pathway. |
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Term
| How can growth factors regulate apoptosis? |
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Definition
Bind to TK receptors and lead to downstream cascade that phosphorylates and activates IAPs, preventing apoptosis (e.g. survival signal).
1) ERK pathway is pro-survival and is activated by GF like NGF
2) JNK pathway is pro-death and is blocked by GF. |
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Term
| Describe the neural organization of ocular dominance |
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Definition
Eye-specific layers of the LGN that receive input from retinal ganglion cells project to layer IV cortical neurons in eye-specfic stripes called ocular dominance columns.
Each layer IV neuron is driven largely by 1 eye or the other. |
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Term
| Describe the major findings of Weisel and Hubels ocular deprivation experiments in cats. |
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Definition
1) Monocular deprivation: you lose binocular and deprived monocular cells
2) Binocular deprivation: you lose responsiveness, but retain distribution of binocular and monocular cells (Relative stimulation is what matters)
3) Strabismus: you lose all binocular cells (TIMING of relative inputs matters for binocular development) |
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Term
| Describe 3 mechanisms that can lead to refinement of synaptic connections. |
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Definition
1) Topography
- Retinal ganglion cell to LGN (eye-specific layers are refined prenatally, while exuberant connections are refined postnatally)
2) Convergence
- Cerebellar PCs receive 1 climbing fiber but TONS of parallel fibers
3) Inhibitory terminals in post-synaptic compartment
- Transistion from axosomatic+ dendritic to axosomatic |
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Term
| How are binocular neuron preferences created? |
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Definition
Local projections from 1 cortical neuron to neighbors.
With strabismus, intracortical circuits become segregated and extend striped pattern throughout entire cortical depth! This disrupts binocular preference |
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Term
| How is inhibition involved in critical periods of visual cortex plasticity? |
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Definition
Rise in inhibition defines end of critical period.
End of critical period is delayed by decreased inhibitory neurotransmission.
Effects of adult monocular deprivation are then more extensive than they would usually be in an adult (very mild) |
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Term
| What is the functional relevance of synaptic refinement for orientation and direction selectivity in the visual system? |
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Definition
1) Vertical goggle rearing increases proportion of neurons responsive to vertical stimuli
2) Strobe light development prevents development of direction sensitivity (static images)
**Dark-reared animals don't develop direction selectivity when eyes are opened, but they do develop orientation sensitivity. Ocular dominance columns are established by spontaneous activity before eyes open** |
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Term
| Describe the function of Reelin in neural development. What happens when it is disrupted? |
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Definition
1) Large ECM protein secreted by CR neurons that facilitates normal brain patterning during development.
- Reelin binds ApoER2 and/or VLDLR and activates the cytoplasmic adaptor protein disabled-1 (DAB-1).
2) Double KO for ApoER2/VLDLR and Dab-1 KO looks like reel in mutation (but distinct neuroanatomical phenotypes)
- Normal ordering in development is inside out, with marginal (pail), upper cortical plate, inner cortical plate, sub plate, intermediate zone (migrating neurons), VZ (white matter boarder).
- In reeler mutant, it is marginal zone, sub plate, inner cortical plate, upper cortical plate, intermediate zone, ventricular zone (outside in) |
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Term
| What unique neuroanatomical features are found in ApoER2 ko mice? |
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Definition
Hippocampi have 2 pyramidal cell layers that can extend from CA1-CA3, depending on where you are along the R-C axis.
- Although these mice had significant neuronal octopi in their hippocampi, they behaved relatively normally, except being more sensitive to stress.
- R-C axis is used to locate coronal sections
- Neurodevelopmental disruptions in the position g of hippocampal pyramidal neurons that vary over the R-C axis can be visualized using saggital sections |
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