Frontal cortical control of an extrathalamic inhibitory pathway projecting to the intralaminar nuclei of thalamus
The intralaminar nuclei of thalamus (IL) is a thalamic node with links to the prefrontal cortex, the cerebellum and the basal ganglia as well. As a consequence the IL has been implicated in higher order motor as well as cognitive functions. Our research group discovered an extrathalamic inhibitory pathway from the pontine reticular formation (PRF) which selectively innervated IL. Photoactivation of PRF-IL fibers evoked complete behavioral arrest and the appearance of a slow cortical oscillation in the frontal LFP for the duration of the stimulation supporting the complex function of IL in organizing behavior. We aimed to examine the cortical inputs of the PRF inhibitory cells in order to assess whether frontal cortex is able to inhibit and/or pattern IL activity via a PRF inhibitory interface. Injections of AAV-ChR2 into the frontal cortex (M2 and Cg) of RBP4-Cre/Glyt2-eGFP double transgenic mice revealed that GlyT2+ neurons of the PRF receives L5 inputs. Juxtacellular recording and labelling in the PRF demonstrated that photoactivation of M2 L5 cells evoked short latency action potentials with high probability in the GlyT2+ cells of the PRF. Spontaneous rhythmic activity of Glyt2+ cells was tightly linked to the slow cortical oscillation and was disrupted upon cortical desynchronization. These data together indicated strong frontal cortical control over the PRF-GlyT2 cells. Our results indicate that frontal cortical regions conveying a behavioral signal and can reliably activate inhibitory neurons of the PRF. PRF GlyT2 cells in turn transfer this to the IL as an inhibitory signal strongly affecting thalamocortical and thalamostriatal activity.