Monosynaptic connection from the subiculum to medial mammillary nucleus neurons projecting to the anterior thalamus and Gudden’s ventral tegmental nucleus

Abstract

As a major hippocampal output structure, the subiculum projects to diverse cortical and subcortical areas, and its projection to the medial mammillary nucleus (MM) has been implicated in memory. Major efferent targets of the MM are the anteroventral and anteromedial thalamic nuclei and Gudden’s ventral tegmental nucleus. These projections may play a key role in distributing subicular information. However, it remains unknown whether neurons in the MM that receive monosynaptic input from the subiculum project to these target regions. We addressed this issue with anterograde transsynaptic tracing mediated using adeno-associated virus serotype 1 (AAV1). Injection of AAV1-Cre and a Cre-dependent AAV encoding enhanced yellow fluorescent protein (EYFP) into the rat dorsal subiculum and MM, respectively, labeled the soma of the MM and axons in the anteroventral / anteromedial thalamic nuclei and Gudden’s ventral tegmental nucleus with EYFP. The EYFP-positive neurons in the MM were immunoreactive for glutamate and leu-enkephalin and received perisomatic GABAergic inputs. These results revealed monosynaptic projections from the subiculum to MM neurons projecting to the anteroventral / anteromedial thalamic nuclei and Gudden’s ventral tegmental nucleus. This monosynaptic connection may support a fast and robust signal flow through the hippocampal–mammillothalamic and hippocampal–mammillotegmental pathways.