Reduced TrkB signalling in Parvalbumin and Somatostatin positive
interneurons have opposite effects on Sensorimotor Gating
Abstract
Parvalbumin-positive interneurons (PV-INs) and Somatostatin-positive
interneurons (SST-INs) have emerged as key players in regulating network
activity and plasticity in both healthy and diseased states. In
particular, research has highlighted the involvement of interneurons in
the development of various psychiatric disorders. We previously showed
that TrkB activity in PV-INs plays a central role in the regulation of
neuronal plasticity. This study investigates the role of TrkB in PV and
SST interneurons and explores the validity of an interneuron-specific
TrkB knockout mouse model. Mice with reduced TrkB expression in either
PV-INs or SST-INs were generated to simulate an abnormal but not
completely absent BDNF/TrkB pathway. By conducting behavioural battery,
we observed that mice with impaired TrkB expression PV-INs exhibited a
significant deficit in the Prepulse inhibition test (PPI), indicating
altered sensorimotor gating. Conversely, TrkB knockout in SST-INs
resulted in an opposite enhanced PPI effect, as well as a significantly
shorter latency to enter the open arm in the elevated plus maze test,
suggesting altered decision-making behaviour. These findings provide
insights into the involvement of the BDNF/TrkB pathway in PV-INs and
SST-INs, supporting the use of heterozygous TrkB knockout models in
studying interneuron plasticity and network dynamics. Moreover, the
altered sensorimotor gating observed in PV-INs highlights the potential
of this model in understanding the sensorimotor abnormalities observed
in schizophrenia.