During the last fiscal year we have completed the majority of work proposed, including anatomical and immediate-early gene activation characterization of the circuit and electrophysiological recordings. The first manuscript reporting these findings is nearly completed and will be submitted within the coming months. In it we report that we have found that the anatomically and physiologically distinct parallel projections from the supramammillary nucleus (SuM) of the hypothalamus to the CA2 and dentate gyrus (DG) hippocampal regions differentially modulate cognition in a task specific manner. Employing immediate-early gene expression labeling, optogenetics and in vivo recordings in a newly developed SuM-Cre transgenic mouse line we find that the SuM to DG circuit is preferentially engaged by spatial novelty while the neurons targeting CA2 are activated by social novelty. As a result, photoinhibition of the SuM-DG projections leads to deficits in recognizing contextual change while photostimulation of the SuM-CA2 circuit impairs the expression of social memory. These data demonstrate that the hypothalamus can play a task-specific role in the encoding and expression of hippocampal memory.
The work has gone very smoothly and several manuscripts are in preparation, including one to be submitted shortly. In addition the support of this grant to the project helped fund a paper published in Science in January 2018.
In the coming year we will extend our studies of the SuM to examine the role of the SuM to medial septum in the regulation of theta oscillations and the performance of spatial working memory tasks.