Mark L. Andermann, Ph.D.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine
Beth Israel Deaconess Medical Center
Linking neural circuits underlying motivation, perception and learning.
Cognitive networks mediating hunger-dependent attention to food cues: Our laboratory seeks to understand how the needs of the body determine which sensory cues are attended to, learned, and remembered. In particular, we are investigating how natural and experimentally induced states of hunger modulate neural representations of food cues, and the consequences for obesity, binge eating, and other eating disorders. Previous studies support a simple model for hunger-dependent processing of food cues: During states of satiety, food cue information enters sensory neocortex but may not flow to cortical areas involved in selective processing of motivationally salient food cues, such as postrhinal cortex (POR). It has been suggested that during states of hunger, POR may be attentionally ‘primed’ such that food cue information spreads from visual cortex through POR to amygdala and on to lateral hypothalamic neurons involved in food-seeking behavior. We are investigating the mechanisms by which genetically, anatomically and chemically defined classes of cortical neurons facilitate cue-induced feeding in a hunger-dependent manner. Such motivation-specific priming of cortical sensory representations may arise from amygdalar and hypothalamic synaptic inputs to cortex, as well as from local hormonal and neuromodulatory actions on specific cortical neurons.
To monitor motivation-related changes in neural activity in the same large populations of neurons across hours, days and weeks, our lab uses two-photon calcium imaging and multi-electrode recordings in behaving mice. The identity of each visualized neuron can be deduced from genetic, anatomical, chemical and immunohistochemical markers. The importance of these cell classes in guiding behavior is then assessed by cell-type and area-specific activation or silencing of neurons using optogenetic and pharmacogenetic approaches. Of critical importance to these efforts, we are developing the hardware and software required for imaging activity of cell bodies and axon terminals from identified projection neurons and from deeper brain structures. We are developing data analysis tools for extracting useful information from these high-dimensional datasets, and for monitoring reactivation of neuronal memory traces and their sensitivity to motivational state. Finally, we hope to incorporate new insights into a broader theoretical and computational neuroscience framework.
Livneh, Y, Ramesh, RN, Burgess, CR, Levandowski, K, Madara, J, Fenselau, H, Goldey, G, Diaz, VE, Jikomes, N, Resch, J, Lowell, BB**, and Andermann, ML** (2017). Homeostatic circuits selectively gate food cue responses in insular cortex. Nature (Article format). DOI: 10.1038/nature22375. Advanced online publication, June 14, 2017. In print: June 28, 2017. **Co-corresponding author. PMCID: PMC5577930.
Burgess, CR*, Ramesh, RN*, Sugden, AU, Levandowski, KM, Minnig, MA, Fenselau, HF, Lowell, BB, and Andermann, ML. Hunger-dependent enhancement of food cue responses in mouse postrhinal cortex and lateral amygdala. Neuron, in press. (* co-first author).
Jikomes, N, Ramesh, RN, Mandelblat-Cerf, Y, and Andermann, ML. Pre-emptive stimulation of AgRP neurons in fed mice enables conditioned food seeking under threat. Current Biology, in press.
Mandelblat-Cerf, Y, Ramesh, RN, Burgess, CR, Patella, P, Yang, Z, Lowell, BB, and Andermann, ML. Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales. eLife 4, (2015).
Glickfeld, LL, Reid, RC & Andermann, ML. A mouse model of higher visual cortical function. Current Opinion in Neurobiology 24, (2014).
Andermann, ML, Gilfoy, N, Goldey, G, Sachdev, R, Wolfel, M, McCormick, D, Reid, RC, & Levene, M. Chronic cellular imaging of entire cortical columns in awake mice using microprisms. Neuron 80, (2013).
Goldey, G, Roumis, D, Glickfeld, LL, Kerlin, A., Reid, RC, Bonin, V., Schafer, D., and Andermann, ML. Removable cranial windows for long-term imaging in awake mice. Nature Protocols 9, (2014).
Glickfeld, LL, Andermann, ML, Bonin, V & Reid, RC. Cortico-cortical projections in mouse visual cortex are functionally target specific. Nature Neuroscience 16, 219–26 (2013).
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