Cortical Development and Mental Disease Flashcards
(25 cards)
Where are cortical pyramidal neurons formed?
Ventricular zone
Where are cortical interneurons formed?
Ganglionic eminence - below developing cortex
What is the effect of RNAi for Lhx6 at the start of corticogenesis?
Very few Lhx6-expressing cells move from the GE into the cortex
What type of migration do interneurons undergo?
Tangential
Which ligand/receptor pair drives interneuron movement from site-of-origin in the GE and what is the role of the ligand?
Slits (ligand) - chemorepellent
Robo (receptor)
Which ligand/receptor pair causes interneurons to bypass the basal ganglia in the GE, what is the role of the ligand, and where is it expressed?
Semaphorins (ligand) - chemorepellent - expressed by striatum
Neuropilins and plexins (receptor)
Which ligand/receptor pair guides interneuron movement into the cortex and what is the role of the ligand?
Neuregulins and SDF-1 (ligand) - chemoattractant
ErbB (receptor)
What is the effect of Robo1 KO in mice?
More interneurons in striatum and cortex
Why do Robo1 KO mice move through the striatum?
Robo1 usually binds directly to Nrp1
Robo1 does not not bind to Nrp1 - decreases Nrp1 and plexinA1 expression - cells not influenced by repulsive action of semaphorins
What type of migration do pyramidal neurons undergo?
Radial migration
What condition is caused by defects in radial pyramidal neuron migration, what are its symptoms, and which genes are implicated?
Lissencephaly - disorganisation of cortical neurons
Mental retardation, epilepsy
LIS1, doublecortin, ARX, reelin
What is the effect of doublecortin RNAi in GE?
Interneurons do not migrate as far - different interneuron distribution within cortex
What are the 2 parvalbumin+ interneurons?
Basket cells
Chandelier cells
Which class of interneurons is linked to SCZ and how?
PV cells
Have decreased GAD67 (GABA synthesis enzyme) in SCZ - reduced ability to inhibit pyramidal neurons
Disturbed integration into cortical circuitry - abnormal gamma frequency oscillations in SCZ PFC
What are the 3 causes of increased pyramidal neuron excitability in SCZ?
Decreased inhibition from PV cells - due to decreased GAD67 in PV cells of dorsolateral PFC
Decreased chandelier cell axon terminals onto pyramidal neurons
Decreased pyramidal neuron projections onto PV cells
What is the effect of Erbb4 KO in PV cells?
In chandelier cells - fewer synapses onto pyramidal cells
In all PV cells - receive decreased input from pyramidal cells
What are the sequential functions of Erbb4 in PV cell development?
Directs migration - in response to NRG1
Controls integration into specific circuits
Which molecule is used to mimic viral infection in a pregnant mouse and what is the response called?
Poly(I:C)
Maternal immune activation (MIA) response
How does MIA in pregnant mouse affect offspring behaviour?
Atypical social and repetitive behaviours - ASD-like
Which molecule secreted into the bloodstream of MIA model mice is required for offspring abnormalities, what secretes it, and what is required for its effect?
IL-17a
Secreted by TH17 cells (immune cells)
Specific intestinal bacteria required for TH17 response to poly(I:C)
Which brain area is responsible for MIA-associated abnormalities?
Dysgranular zone - in somatosensory cortex
What is the effect of optogenetically stimulating the dysgranular zone in offspring of mice that had not undergone MIA?
Caused atypical social and repetitive behaviours
What is the effect of optogenetically inhibiting the dysgranular zone in offspring of mice that had undergone MIA?
Stopped atypical behaviour
Which projection from the dysgranular zone causes the atypical social behaviour?
Temporal association area
