Neural Circuits and Systems Neuroscience
Author: Diego Esteban Pafundo | email: dpafundo@fmed.uba.ar
Diego E Pafundo 1°, Carlos A Pretell Annan 1°, Nicolás M Fulginiti 1°, Juan E Belforte 1°
1° Grupo de Neurociencia de Sistemas, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO-Houssay), UBA-CONICET, Buenos Aires, Argentina.
Schizophrenia (SZ) is a devastating disease characterized by cognitive disorders. Inputs from distal regions to the prefrontal cortex such as the ventral hippocampus (vHP) are important for cognition, and deficits in the vHP-prefrontal connection are found in patients. Parvalbumin positive interneurons (PVin) function and connectivity are crucial for normal circuits function and their disfunction is associated with cognitive deficits in SZ. Furthermore, the reciprocal synapses between PVins and pyramidal neurons (PNs) can control local activity by feedback and feedforward inhibition (FFI). In the latter, inputs recruit PNs and interneurons and thus have important consequences for synaptic integration. Inputs from the vHP directly synapse both PNs and PVins in the mPFC, thus altered vHP-mPFC connectivity may disrupt mPFC function in a complex manner. Knowing the relative synaptic strength to these neurons is crucial to understand circuit disfunction in SZ. Here we use a mouse model where the NMDA receptor is eliminated from corticolimbical interneurons during early postnatal development that shows functional and structural deficits in the prefrontal circuit as well as a vHP-mPFC disconnection and behavioral impairments compatible with SZ. We found that the relative strength of vHP-mPFC inputs to PVins and PV is altered in the KOs reducing the effect of FFI in a specific manner since the relative callosal mPFC-mPFC connections to PNs and PVins remain unaltered in the KOs.