Thalamic microcircuits: presynaptic dendrites form two feedforward inhibitory pathways in thalamus

In the visual thalamus, retinal afferents activate both local interneurons and excitatory thalamocortical relay neurons, leading to robust feedforward inhibition that regulates the transmission of sensory information from retina to neocortex. Peculiarly, this feedforward inhibitory pathway is dominated by presynaptic dendrites. Previous work has shown that the output of dendritic terminals of interneurons, also known as F2 terminals, are regulated by both ionotropic and metabotropic glutamate receptors. However, it is unclear whether both classes of glutamate receptors regulate output from the same or distinct dendritic terminals. Here, we used focal glutamate uncaging and whole cell recordings to reveal two types of F2 responses in rat visual thalamus. The first response, which we are calling a Type-A response, was mediated exclusively by ionotropic glutamate receptors (i.e., AMPA and NMDA). In contrast, the second response, which we are calling a Type-B response, was mediated by a combination of ionotropic and type 5 metabotropic glutamate receptors (i.e., mGluR(5)). In addition, we demonstrate that both F2 responses are evoked in the same postsynaptic neurons, which are morphologically distinct from neurons in which no F2 responses are observed. Since photostimulation was relatively focal and small in magnitude, these results suggest distinct F2 terminals, or small clusters of terminals, could be responsible for generating the two inhibitory responses observed. Because of the nature of ionotropic and metabotropic glutamate receptors, we predict the efficacy by which the retina communicates with the thalamus would be strongly regulated by 1) the activity level of a given retinogeniculate axon, and 2) the specific type of F2 terminals activated.