Andrew Holmes

NIAAA, NIH, USA

Biography

Andrew Holmes is chief of laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health.

In his work, dr Holmes focuses on understanding the causes of alcoholism and comorbid neuropsychiatric conditions such as mood and anxiety disorders. The approaches vary from analysis of behavior to neuronal firing and gene networks, all aimed to provide the most detailed understanding of this complex research problem. Moreover, the emphasis is also heavily put on the individual differences, including genetic factors as well as the role of the environment, sex and age. Dr Holmes’s contributions to our understanding of the prefrontal cortex to limbic and dorsal striatal circuits, which are known to be critical for the regulation of emotion, cognition and executive control over drug-seeking are of great importance which is reflected by him being the author of over 150 scientific articles.

The group’s recent publications cover the topics of neural substrates for endocannabinoid modulation of fear extinction, and prefrontal regulation of punished ethanol self-administration. Dr Holmes is also involved in the popularization of science which his TED Talk Emotionome, How emotion creates brain states is a great example of.

Talk: "Non-canonical mechanisms underlying amygdala mediated memory representation"

Brain systems mediating responses to previously encountered threats are critical to animals’ survival. While learned threats have been shown to generate neural representations of fear state in the basolateral amygdala (BLA), the contribution of non-neuronal cells to this process remains unclear. Here, employing a combination of in vivo calcium (Ca2+) imaging and chemogenetics, we demonstrate that BLA astrocytes track fear state and causally contribute to cued fear memory retrieval. Then, by performing in vivo cellular-resolution neuronal Ca2+ imaging and electrophysiological recordings, we show dynamic astrocyte Ca2+ activity enables fear-cue BLA neuronal encoding and supports fear state neural representation by enriching the amount of motivationally-relevant information contained in the neuronal population. Our findings reveal a key role for astrocytes in memory retrieval through amygdala neural representation of fear state, revising current neurocentric models of an essential survival function.

Selected Publications

Silverstein SE, O'Sullivan R, Bukalo O, Pati D, Schaffer JA, Limoges A, Zsembik L, Yoshida T, O'Malley JJ, Paletzki RF, Lieberman AG, Nonaka M, Deisseroth K, Gerfen CR, Penzo MA, Kash TL, Holmes A (2024). A distinct cortical code for socially learned threat. Nature. 2024 Feb;626(8001):1066-1072 PMID: 38326610

Gunduz-Cinar O, Castillo LI, Xia M, Leer E, Brockway ET, Pollack GA, Bukalo O, Limoges A, Oreizi-Esfahani S, Kondev V, Báldi R, Dong A, Harvey-White J, Cinar R, Kunos G, Li Y, Zweifel LS, Patel S, Holmes A (2023). A cortico-amygdala circuit substrate for endocannabinoid modulation of fear extinction. Neuron 111: 3053-3067.

Hagihara KM, Bukalo O, Zeller M, Aksoy-Aksel A, Karalis N, Limoges A, Rigg T, Campbell T, Mendez A, Weinholtz C, Mahn M, Zweifel LS, Palmiter RD, Ehrlich I, Lüthi A, Holmes A (2021). Intercalated amygdala clusters orchestrate a switch in fear state. Nature 594:403-407.

Bukalo O, Pinard CR, Silverstein S, Brehm C, Hartley ND, Whittle N, Colacicco G, Busch E, Patel S, Singewald N, Holmes A (2015). Prefrontal inputs to the amygdala instruct fear extinction memory formation. Science Advances 1:e1500251.

Halladay LR, Kocharian A, Piantadosi PT, Authement M, Lieberman AG, Coden K, Spitz NA, Glover L, Costa VD, Alvarez V, Holmes A (2020). Prefrontal regulation of punished ethanol self-administration. Biological Psychiatry 87:967-968.

Sengupta A, Holmes A (2019). A discrete dorsal raphe to basal amygdala 5-HT circuit calibrates aversive memory. Neuron 103:489-505.