Schizophrenia Flashcards

Question

How does the Pyramidal neuron-parvalbumin GABA neuron circuitry in the DLPFC layer 3 work?

Answer 1

I think there's excitatory input to the PYR cell which passes through the PV cell and inhibits another PYR cell. This then excites the PV cell some or the original PYR cell. The second PYR cell can also be directly excited by the first. This is all through glutamate.

Answer 2

In the DLPFC, pyramidal neu- rons (Figure 1C) are the principal source of glutamate neurotransmission, as well as the targets of the majority of glutamate-containing axon terminals.

Answer 3

Neuronal density. Increased cell packing density has been interpreted as evidence of a reduction in the amount of cortical neu- ropil, the axon terminals, dendritic spines, and glial processes that occupy the space between neurons.

Answer 4

Dendritic spines are the principal targets of excitatory synapses to pyramidal neurons. Although most dendritic spines present are stable in number during adulthood,23 they are subject to a number of neuroplastic changes, such as a loss of their presynaptic excitatory input. In schizophrenia, dendritic spine density in pyramidal neu- rons has been reported to be lower in the DLPFC24,25

Answer 5

For example, many pyramidal cells in layers 2 to 3 send axonal projections to other cortical regions, pyramidal neurons in layer 5 tend to project to the striatum and other subcortical structures, and pyramidal neurons in layer 6 furnish projections primarily to the thalamus.26 Studies of basilar dendritic spine density on Golgi-impregnated pyramidal neurons in each cortical layer of the DLPFC in the same cohort of subjects found a significant effect of diagnosis on spine density only for pyramidal neurons in deep layer 3 (Figure 2).25,27 In schizophrenia, somal bodies are smaller in deep layer 3, but not layer 5. The decrease indicates fewer dendritic spines

Answer 6

Thus, the presence of functionally mature synapses prior to adolescence supports the hypothesis that the excess in excitatory synapse number prior to adolescence might be able to compensate for a molecu- lar based dysfunction of these synapses in individuals with schizophrenia, and thereby forestall the appearance of the clinical features of the illness until synapse num- ber falls below some critical threshold.

Answer 7

Synthesis and reuptake are lower in the DLPFC

Answer 8

IPSC duration (inhibitory post synaptic current)

Answer 9

Synchronized network oscillations.

Answer 10

It's impaired. PV Basket Neuron doesn't seem to inhibit pyramidal neurons as well.

Answer 11

1) Lower presynaptic strength of inhibition due to less GABA (less protein that makes GABA in terminals) 2) Lower postsynaptic strength of inhibition due to fewer GABA receptors 3) Cl- Less hyperpolarization due to lower CI- influx when GABA receptors open

Answer 12

More synchrony in DLPFC during short term retention of information for a cognitive task. Doesn't look normal but better than maybe first-degree relatives.

Answer 13

Problem with excitatory drive in pyramidal neurons.

Answer 14

Spine deficits in the DLPFC are upstream of subcortical hyperdopaminergia and this results in psychosis over time. Less GABA disinhibits dopamine and causes psychotic impairment.