McHugh Thomas （RIKEN BRAIN SCIENCE INSTITUTE）
Divergent Information Routing by a Hypothalamo-Hippocampal Circuit
The hippocampus is critical for memory formation and spatial navigation. Neurons in the rodent hippocampus have been shown to robustly encode spatial locations and depending on the task demands, can flexibly encode other cues as well, including odors, time and even social identity. Connecting these neuronal representations with behavior requires understanding how the information is used for successful goal-directed behavior. The supramammillary nucleus (SuM) of the hypothalamus is activated by novelty and stress, is involved in spatial learning and influences the hippocampal theta oscillations. While anatomical studies have described direct projections from the SuM to CA2 and the dentate gyrus (DG) in the hippocampus, the physiological and behavioral consequences of their activation is missing. We have developed a SuM-Cre transgenic mouse in the lab that allows the use of an array of techniques for circuit interrogation, including optogenetics-based behavioral testing and in vivo recordings. We have established that the projections to CA2 and the DG originate from anatomically distinct regions of the SuM and have differential impacts on behavior. Further, using projection specific optogenetic manipulations we have shown that activation of the SuM to CA2 projection impairs social memory while inhibition of the SuM to DG projection impairs spatial working memory. In this project we will are integrating genetic, behavioral and physiological approaches to understand how the hypothalamic-hippocampal circuit modulates flexible behavior.
1. Boehringer R, Polygalov D, Huang AJY, Middleton SJ, Robert V, Wintzer ME, Piskorowski RA, Chevaleyre V, McHugh TJ. (2017) Chronic loss of CA2 transmission leads to hippocampal hyperexcitability. Neuron, 94(3):642-655.
2. Middleton SJ and McHugh TJ. (2016) Silencing CA3 disrupts temporal coding in the CA1 Ensemble. Nature Neuroscience, 19(7): 945-951.
3. Miyamoto D, Hirai D, Fung CCA, Inutsuka A, Odagawa M, Suzuki T, Boehringer R, Adaikkan C, Matsubara C, Matsuki N, Fukai T, McHugh TJ, Yamanaka A, Murayama M. (2016) Top-Down Cortical Input during NREM Sleep Consolidates Perceptual Memory. Science, 352(6291): 1315-1318.
4. Yu LMY, Polygalov D, Wintzer ME, Chiang MC, McHugh TJ. (2016) CA3 synaptic silencing attenuates kainic acid induced seizures and hippocampal network oscillations. eNeuro, 3(1), http://dx.doi.org/10.1523 /ENEURO.0003-16.2016
5. Tomar A, Polygalov D, Chattarji S, McHugh TJ. (2015) The dynamic impact of repeated stress on the hippocampal spatial map. Hippocampus, 25(1): 38-50.