Lopes-Aguiar, C. | Search bioRxiv

bioRxiv2020

A critical role for trkB signaling in the adult function of parvalbumin interneurons and prefrontal network dynamics

Inhibitory interneurons expressing parvalbumin (PV) in the prefrontal cortex (PFC) are central to excitatory/inhibitory (E/I) balance, generation of gamma oscillations, and cognition. Dysfunction of PV interneurons disrupts information processing and cognitive behavior. Tyrosine receptor kinase B (trkB) signaling is known to regulate the differentiation and maturation of cortical PV interneurons during development, but is also suggested to be involved in the activity and network functions of PV interneurons in the adult brain. Using a novel viral strategy for cell-type and region-specific expression of a dominant negative trkB in adult mice, we show that reduced trkB signaling in PV interneurons in the PFC leads to pronounced morphological, physiological, and behavioral changes. Our results provide evidence for a critical role of trkB signaling in the function of PV interneurons in the adult brain, local network activities central to prefrontal circuit dynamics, and cognitive behavior.

neuroscience↗

bioRxiv2019

Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo

N-methyl-D-aspartate receptor (NMDAr) antagonists such as ketamine (KET) produce psychotic-like behavior in both humans and animal models. NMDAr hypofunction affects normal oscillatory dynamics and synaptic plasticity in key brain regions related with schizophrenia, particularly in the hippocampus and the prefrontal cortex. In contrast, long-term potentiation (LTP) induction is known to increase glutamatergic transmission. Thus, we hypothesized that LTP could mitigate the electrophysiological changes promoted by KET. We recorded HPC-PFC local field potentials and evoked responses in urethane anesthetized rats, before and after KET administration, preceded or not by LTP induction. Our results show that KET promotes an aberrant delta-high-gamma crossfrequency coupling in the PFC and an enhancement in HPC-PFC evoked responses. LTP induction prior to KET attenuates changes in synaptic efficiency and prevents the increase in cortical gamma amplitude comodulation. These findings are consistent with evidence that increased efficiency of glutamatergic receptors attenuates cognitive impairment in animal models of psychosis. Therefore, high-frequency stimulation in HPC may be a useful tool to better understand how to prevent NMDAr hypofunction effects on synaptic plasticity and oscillatory coordination in cortico-limbic circuits.

neuroscience↗