VTA multifaceted modulation of CA1 local circuits

Abstract

Excitatory pyramidal (PYR) cell activation of interneurons (INT) produces network oscillations that underlie cognitive processes in the hippocampus (CA1). Neural projections from the ventral tegmental area (VTA) to the hippocampus contribute to novelty detection by modulating CA1 PYR and INT activity. The role of the VTA in the VTA-hippocampus loop is mostly attributed to the dopamine neurons although the VTA glutamate-releasing terminals are dominant in the hippocampus. Because of the traditional focus on VTA dopamine circuits, how VTA glutamate inputs modulate PYR activation of INT in CA1 neuronal ensembles is poorly understood and has not been distinguished from the VTA dopamine inputs. By combining CA1 extracellular recording with VTA photostimulation in anesthetized mice, we compared the effects of VTA dopamine and glutamate input on CA1 PYR/INT connections. Stimulation of VTA glutamate neurons shortened PYR/INT connection time without altering the synchronization or connectivity strength. Conversely, activation of VTA dopamine inputs delayed CA1 PYR/INT connection time and increased the synchronization in putative pairs. Taken together, we conclude that VTA dopamine and glutamate projections produce tract-specific effects on CA1 PYR/INT connectivity and synchrony. As such, selective activation or co-activation of these systems will likely produce a range of modulatory effects on local CA1 circuits.

Keywords: CA1; Dopamine; Glutamate; Interneuron; Pyramidal; Synapse; VTA.