Optogenetic stimulation of septal somatostatin neurons disrupts locomotory behavior and regulates hippocampus cholinergic theta oscillations

Abstract

The septal complex regulates both motivated and innate behaviors, chiefly by the action of its diverse population of long-range projection neurons. Among those cells are lateral septum somatostatin neurons which collateral axons profusely innervate cortically-projecting neurons located in the medial septum. Thus, somatostatin cells are ideally positioned at the crossroads of ascending and descending modulatory pathways, likely supporting functional roles in both anatomical directions. Here, we used optogenetic stimulation and extracellular recordings in acutely anesthetized transgenic mice to show that septal somatostatin neurons can disinhibit the cholinergic septo-hippocampal pathway, thus enhancing the amplitude and synchrony of theta oscillations, while depressing sharp wave ripple episodes in the dorsal hippocampus. Nonetheless, photosuppressing septal somatostatin cells hindered goal-directed behavior in a spatial memory task by disrupting task engagement, evidenced in increased immobility, followed by repetitive self-grooming, a hallmark innate behavior. These results suggest that septal somatostatin cells can recruit ascending cholinergic pathways to promote hippocampal theta oscillations, while gating repetitive displacement behaviors mediated by descending subcortical pathways. Significance StatementA small population of somatostatin-expressing GABAergic cells in the lateral septum projects deep into subcortical regions, yet on its way it also targets neighboring medial septum neurons that profusely innervate cortical targets. We show here that selective inhibition of septal somatostatin cells exerts significant consequences in both ascending and descending synaptic pathways. Indeed, cortical targets increased the expression of hippocampal theta oscillations, which are relevant for sensorimotor processing, temporal coding, and a marker of anxious behaviour; whereas subcortical targets triggered repetitive self-grooming, an innate displacement behaviour. Our results suggest that septal somatostatin cells are a potential target for the control of altered innate behaviors in translational neuroscience.