02 Cortical Interneurons Flashcards
1
Q
How many neurons/minute are generated during proliferation peak?
A
- 250,000 neurons/min generated during proliferation peak
- cell division for excitatory neurons (mainly pyramidal cells) takes place
2
Q
What are the 2 types of cell division?
A
neural stem (= precursor) cells divide
- symmetrically (early stage): two new stem cells
- asymmetrically (later stage): one stem cell, one post-mitotic neuroblast (immature nerve cell)
3
Q
Where does cell division take place for excitatory neurons? What happens to the neuroblasts?
A
- close to ventricles (ventricular zone)
- neuroblasts migrate from there to the surface
4
Q
What are radial glia cells?
A
- intermediate morphology of (some?) neuroblasts, spanning from VZ to surface
- serve as scaffold for other neuroblasts to migrate along
- subsequently develop into mature neurons themselves
5
Q
proportion excitatory and inhibitory cortical neurons
A
- 70-80% excitatory
- 20-30% inhibitory
6
Q
What are excitatory neurons?
A
- synomynous with projection neurons
- long axons targeting other cortical areas or non-cortical structures (basal ganglia, thalamus, spinal cord, etc.), mediating communication between brain areas
- main neurotransmitter: glutamate
- migration from VZ along radial glia to surface applies to development of excitatory cortical neurons only
7
Q
What are inhibitory neurons?
A
- synonymous with “interneurons”
- short axons targeting local cells, regulating activity of nearby projection neurons and interneurons (local computation)
- main neurotransmitter γ amino butyric acid (GABA) / GABAergic
- originate in ganglionic eminences of subpallium
8
Q
Structure of early embryonic brain
A
- telencephalon consists of pallium and
subpallium
pallium: - future cortex (allocortex and isocortex), amygdala, and claustrum
- neurogenesis of glutamatergic projection neurons, radial migration from VZ towards surface
subpallium: - future striatum , pallidum, and other nuclei
- neurogenesis of inhibitory cortical neurons
9
Q
ganglionic eminences
A
- protrusions expanding into the ventricle
- lateral ganglionic eminence (LGE) spawns cells of olfactory bulb and striatum
- medial (MGE, Basket, Chandelier, Translaminar cells) and caudal (CGE, Basket, Bipolar cells, etc.) spawn different types of cortical interneurons
- 3 major IN groups defined by histochemical criteria (staining for specific substances)
10
Q
types of cortical interneurons
A
- 3 major groups according to presence of parvalbumin (PV), somatostatin (SST), or 5HTR3a serotonin receptors
- interneuron synapses onto projection neurons
- synapses closest to axon hillock exert greates inhibition of PN output (chandelier cells target axon hillock itself)
- more distal synapses (on dendrites) contribute to computation within PN
11
Q
characteristics of parvalbumin-positive interneurons
A
- approx. 40% of cortical INs
- basket cells: found across layers, target soma and proximal dendrites of PN and IN
- chandelier cells: mostly in layers VI and II, inhibit axon initial segment hillock) of local PN
- translaminar cells: in deep cortical layers, axons traverse all layers, with supposed role as “general gain modulators” of the entire column
12
Q
characteristics of somatostatin-positive interneurons
A
- approx. 30% of cortical INs
- Martinotti cells: mostly in layers II/III and V, but send axons to layer I, inhibiting dendrites of PN and other INs (recall: layer I mainly contains axons and dendrites coming from deeper layers)
- Non Martinotti cells: local axons, found across all layers, but especially rich in layer IV
13
Q
characteristics of serotonin receptor 5HTR3a expressing cortical interneurons
A
- approx. 30% of cortical INs
- “diverse conglomerate of cell types with different laminar distribution, morphologies, functional properties, and connectivity patterns”
- mostly in superficial layers II/ III (recall: intracortical communication)
14
Q
Neurogenesis and migration of INs
A
- somatostatin+ cells peak proliferation during early embryonic phase
- parvalbumin+ cells produced in more extended and continuous fashion
- temporal dynamics of 5HRT3a neurons less understood
- nascent interneurons begin to migrate towards cortex guided by attractants while circumventing the striatal area, which expresses repellants
- within cortex, interneurons first migrate tangentially (parallel to surface) to destined area, before allocating radially to correct layer
15
Q
Settling within cortex of INs
A
- once within the cortex (pallium), migratory INs cannot return to subpallium
- attractants secreted by PN (projection neurons) draw them to final location within cortex
- similar to PN, there appears to be an inside-out (or inside-out-in) laminar maturation
- CGE (caudal gang. em.)-derived cells laminar distribution depends on serotonin-signaling, with deficiencies during development leading to increase in anxiety, depression, or autism-like behavior in rodents
- after arrival at final destination, INs begin to synapse onto neighboring neurons (PNs and INs) and initiate neuronal activity, prompted by thalamic input
- 30-40 % of INs undergo programmed cell death after settling (cf. 12 % of PNs), which is prevented in some IN subtypes by strong input from PNs
- how IN axons find specific targets is largely unknown, but seems to depend on glia
