Psychiatric disorders related to integrity of hippocampal area CA2
A mouse model of 22q11.2 deletion syndrome shows unique alterations in area CA2 of the hippocampus and social memory deficits. The results of a study from Paris Descartes and Columbia Universities shows this region of the brain may play a significant role in some psychiatric and neurodevelopmental disorders. This pharmacologically unexplored area could be a potential therapeutic target for psychiatric diseases.
22q11.2 deletion syndrome affects an estimated 1 in 4,000 people and is a genetic risk factor for several neuropsychiatric disorders, including schizophrenia. The transatlantic collaborators, who recently published a paper on their findings in Neuron, used the Df(16)A+/- mouse model of the syndrome to examine how area CA2 is altered in psychiatric illness. Numerous post-mortem studies of schizophrenic and psychotic patients have shown that the CA2 region undergoes disease-related changes in size and composition, but the local cellular changes in the hippocampal microcircuit are unknown.
Interestingly, the onset of neuropsychiatric disorders in 22q11.2 deletion syndrome is age-dependant. In late adolescence and early adulthood, up to one-third of individuals carrying the deletion develop schizophrenia and schizoaffective disorder.
The main findings of this paper established that adult Df(16)A+/- have:
- A reduced density of parvalbumin-expressing (PV+) interneurons in the CA2
- A significant decrease in the age-dependant level of feedforward inhibitory transmission onto CA2 pyramidal neurons (PNs)
- A more hyperpolarised resting membrane potential and decreased action potential firing in CA2 PNs
- Strongly impaired social memory
These results demonstrate that CA2 PNs are effectively silenced in this model of 22q11.2 deletion syndrome. CA2 PNs project to multiple brain regions outside the hippocampus and the modified output from these neurons is likely to have significant effects on long-range connections.
Area CA2 is altered in a number of disorders including schizophrenia, bipolar disorder and neurodegenerative diseases. It is possible that an improperly functioning CA2 brain region upsets the fine tuning between primitive drives and higher cognitive functions, leading to cognitive dysfunction.
Further studies of the CA2 region in animal models of psychiatric disorders may help to elucidate more of the underlying neural circuitry responsible for the symptoms associated with these conditions.
Electrophysiological experiments were carried out on a number of SliceScope Pro systems, including an upright microscope and motorised micromanipulators
Paper Reference:
Piskorowski R.A., Nasrallah K., Diamantopoulou A, Mukai J., Hassan S.I., Siegelbaum S.A., Gogos J.A., Chevaleyre V. Age-dependent specific changes in area CA2 of the hippocampus and social memory deficit in a mouse model of the 22q11.2 deletion syndrome Neuron (2016) doi: 10.1016/j.neuron.2015.11.036
Banner image credit: Columbia University Medical Center
)