Development p2 Flashcards
What is the result of alcohol when pregnant
Reduced proliferation of progenitor cells, increased cell death in VZ
Small brain volume
What is the result of cannabis when pregnant
Feotal growth restriction, mental dysfunction (memory impairment, social difficulty)
What is the result of cocaine when pregnant
Inhibits tangential and radial migration, long-term consequences for DA transporter function
In what order are different combinatorial transcriptino codes expressed
Reelin, Tbr1, SCIP, GABA, Brn2
What transcription factor speciices supragranular layer neurons
SATB2
What transcription factor speciices layer 5 neurons
CTIP2
What transcription factor specifices subplate neurons
SOX5
Where are growth cones
Tip of advancing axon
What is netrin
A diffusible molecular guidance molecule- atrracts some neuronal populations and repels others
Axons extend well past their targets during development and then…
Form collaterals that connect with their target
Excess length/colaterals are then eliminated through degeneration
An example of large-scale axon elimination
Develops area-specific projections of layer 5 neurons of the neocortex
What happens to our proportion of grey vs white matter as we get older
Less grey matter as we grow from age 4-21
What difference in gray vs white matter happens in schizophrenia
Dynamic wave of accelerated gray matter loss
Environmental prenatal factors associated with schizophrenia
Maternal nutrition and infection, season of birth, urban birth, small head size
Summarise how ocular dominance columns are formed
The 2 monocular inputs are initially overlapped, and gradually segregate by selective local pruning driven by competition betweeen correlated neural activity
How do glutamatergic cells migrate
Radially from ventricular zone to cortical plate
How do GABAergic cells migrate
Tangentially from the ganglionic eminence to CTX
What results from leading edge extension defecits in cell migration
Mixed up collectino of cells that don’t leave the subventricular zone- paraventricular heterotopia
What is type 1 lissencephaly
Subplate and preplate split properly, but superficial layers pile up- partially developed cortex
What is type 2 lissencephaly
Cells don’t stop migrating outwards past the pial membrane,shape of brain altered
What is the result of a defective reelin pathway
Subplate and marginal zone don’t split into layers, but stay together as a super plate, cortical plate develops in a backwards outide-first fashion
What is the subplate
Subplate cells are very important as a dynamic scaffold during devellopment, but die off and aren’t present in the fully developed in the fully developed brain
In what 3 ways can growth cones be powered
By movement of actin along myosin
By assembly of actin monomers into polymeric filaments
By slowing depolymerisation of actin filaments
What molecule in the growth cone drives it forward
Microtubules flow from the central core into the newly extended tip
In what ways can ligand binding to recptors affect growth
Stimulates formatino of second messengers that affect cytoskeletal organisation
Regulating Ca2+ conc, motility is optimal within a narrow range of conc
Modulating enzymes that regulate proteins that regulate actin polymerisation
What is the idea of molecular matching
Recognition between axons and their targets relies on molecular matching- usually pairs of ligands along the pathway and receptors on the growth cone
How can we describe the first axons travelling up the optic nerve to the brain
Pioneer axons- act as scaffolds for later-arriving axons
Respond to molecular cues along the way
What protein-ligand combo can act by forming gradients to guide axonal growth
Eph kinases are receptors, ephrins are membrane-associated ligands
eg ephrin-A proteins bind and activate EphA kinase
What map to ephrins and Eph kinases set up
Retinotopic map in the tectum
eg ephrinA grades from anterior-low to posterior-high in the tectum, counter Eph receptor gradient in the retina
How can inappropriate targets be turned into appropriate ones in skeletal muscle
Motor axons can convert the target muscle fibre into an appropriate type before the fibre’s properties are fixed eg slow -> fast by the axon’s firing
What are the possible benefits of initial polyneuronal innervation
Ensures all muscle fibres are innervated, allows all axons to capture an appropriate set of target cells, means activity can change the stregnth of specific synaptic connections
What is likely to determine the outcome of synapse competition in muscle fibres
The total amount of synaptic that the axon provides the muscle with- when a fibre is not very active, it is likely to withdraw, and redistribute its resources
What cooperative firing is likely to establish ocular dominance columns
Neighbouring axons from one eye tend to fire together (activated by same stimuli), so cooperate in depolarising a target cell, strengthening these synapses at the expense of non-cooperating synapses
Hubel and Wiesel experiment about temporal activity affecting competition vs cooperation
Made cats strabismic- binocular cells became monocular instead, suggesting disrupting the synchrony of inputs led to competition rather than competition
Where do the first physiological changes occur following closing of one eye
In layers II/III and V of V1 (local circuitry), rather than thalamic input- suggests loss of cortical responsive results from circuit alteration NOT loss of input
What 3 changes of cell functino have been suggested as underlying the circuitry changes in V1 durnig optical deprivation
Excitatory synapses decrease in strength (LTD)
Inhibitory synapses become stronger, decreasing the level of excitation caused by closed eye input
Turning the circuit to favour LTD
What neurotransmiter signalling appears inolved in monocular depviration
The critical period for changes from deprivation can be advanced by enhancing GABA signalling, and delayed by delaying GABA signalling
What is the appearance and loss of dendritic spikes thought to reflect
Formation and elimination of synapses- increased spine no is associated with behavioural changes
Describe the progression of dendritic spikes during monocular deprivation /remapping of stronger eye
Spine no increases 2 days after eye closrure, suggesting synapses are rearranging
Spine no decreases due to loss of inputs from closed eye
Spine increase occurs as responsiveness to open eye increases
Example for how alteratinos in V1 synaptic strength may affect V1 input from LGN?
V1 activity may regulate the secretion of BDNF (brain deprived neurotrophic factor), which enhances thalamocortical growth and speeds up maturatino of inhibitory circuits, regulating axonal survival
What physiological change may underlie the closing of the critical period
Myelination of axons occurs when the critical period closes- creates physical barriers to sprouting and axonal growth, and contanis factors like Nogo that inhibit axonal growth
How does segregation of retinal input in the LGN differ from that in the cortex
In LGN, segregation of input is complete before birth
How does segregatino of LGN input occur in utero
Retinal neurons fire spontaneously, with neighoburing ganglion cells firing in synchronous bursts
These bursts spread across the retina as waves, exciting a local group of LGN neurons, strengthening these synapses at the expense of others
How does the pattern of activity on the light refine the topographic map on the tectum
When light falls haphazardly on the retina (as normally), it produces local synchronous activity of neighbouring ganglion cells- the tectum deetrmines which retinal axons are neighbours by judging which fire in synchrony
