My research aims at a biophysically grounded, mechanistic understanding of the neuronal processes in the mammalian brain that underlie adaptive behavior, including associative learning, short- and long-term memory, and decision making. In our lab, we use the mouse as a model organism to link synaptic, cellular, circuit, and system function to evolutionarily conserved adaptive behaviors under both normal and pathological conditions, such as neuropsychiatric (e.g., schizophrenia) and neurodevelopmental disorders (e.g., autism spectrum disorders). My previous experimental work focused on the subregion CA2 of the hippocampus, a critical hub that integrates social sensory information to support social memory – the ability to remember a conspecific. We identified a pathophysiological upregulation of TREK-1 mediated potassium currents in CA2 excitatory cells in a mouse model of the 22q11.2 syndrome, the highest known risk factor for psychosis in humans (Piskorowski,…,Hassan et al., Neuron 2016); the increased potassium conductance in CA2 excitatory cells was causally linked to social memory deficits in this model. In an independent line of experiments, I used large-scale multiphoton imaging of CA2 activity in vivo to understand its network function underlying the encoding of individual social stimuli (i.e., urine from conspecific mice). Our work revealed for the first time highly robust odor tuning in CA2 and higher-order network structure that allows CA2 to perform complex classification and categorization.
Our current research expands on these findings of CA2 being a powerful hub in organizing multidimensional social features into a coherent abstract social map and its critical role in disease. In addition, our research question more generally aims to understand how the hippocampus as a whole transforms multimodal cortical information into a coherent representational model that serves adaptive behavior; a focus will stay on the social context and further explore potential implications for neurodevelopmental disease. More specifically, we seek to dissect how excitatory, inhibitory, and neuromodulatory circuit motifs contribute to these functions. To achieve this, we employ large-scale, subcellular-resolution in vivo functional imaging alongside electrophysiology, cell-type-specific manipulations, in vitro experiments, and computational modeling, to provide mechanistic insights into experimental findings ranging from the algorithmic to the implementation level.

My following publications exemplify our scientific approach:

1. Piskorowski, R.A., Nasrallah, K., Diamantopoulou, A., Mukai, J., Hassan, S.I., Siegelbaum, S.A., Gogos, J.A., and Chevaleyre, V. (2016). Age-Dependent Specific Changes in Area CA2 of the Hippocampus and Social Memory Deficit in a Mouse Model of the 22q11.2 Deletion Syndrome. Neuron 89, 163–176. https://doi.org/10.1016/j.neuron.2015.11.036.
2. Hassan, S.I., Bigler, S., and Siegelbaum, S.A. (2023). Social odor discrimination and its enhancement by associative learning in the hippocampal CA2 region. Neuron 111, 2232-2246.e5. https://doi.org/10.1016/j.neuron.2023.04.026.