The role of dentate gyrus somatostatin-expressing cells in pattern separation

Abstract

Pattern separation, which is a mechanism that takes place in Dentate Gyrus (DG), would allow the discrimination of similar episodic memories by increasing the differences of synaptic inputs that reach DG. Disruptions of this memory discrimination have been related to cognitive impairment in aging, neuropsychiatric disorders, and epilepsy. The excitability regulation of DG is critical, as evidenced by deteriorated pattern separation when this excitability is experimentally enhanced. Somatostatin containing cells (SOM+), a type of GABAergic interneurons of DG are good candidates to control the excitatory inputs reaching DG, but its role in controlling the flow of information in the dentate gyrus circuitry remains elusive. In this thesis I tested the hypothesis that functional SOM+ are required for contextual discrimination through the control of DG excitability. For that purpose, I studied the effect of inhibition of SOM+ in DG excitability in anesthetized mice. Then, in a second experiment, in awake mice I studied the effect of inhibition of SOM+ in behavioral tasks that need the pattern separation mechanism. I found out that optogenetic suppression of SOM+ modulated the firing rate of putative excitatory cells and putative Parvalbumin containing cells (PV+), other type of GABAergic interneurons. Moreover, optogenetic stimulation impaired both contextual and spatial discrimination of overlapping recognition memories during task acquisition. These results suggest that SOM+ are required for successful pattern separation during episodic memory encoding. Indicating that SOM+ must be considered in future model of pattern separation mechanism. Specifically, I propose that SOM+ command a delayed feedback inhibition.