Andrew Holmes

Astro­cytes gate the recall of emo­tion­al fear memory

Abstract

Brain sys­tems medi­at­ing behav­ioral respons­es to pre­vi­ous­ly encoun­tered threats are crit­i­cal to ani­mals’ sur­vival. The baso­lat­er­al amyg­dala (BLA) medi­ates the expres­sion of fear mem­o­ry, but the con­tri­bu­tion of BLA astro­cytes to fear remains unclear. Employ­ing in vivo cal­ci­um imag­ing, we found that BLA astro­cytes dynam­i­cal­ly track behav­ioral fear state and, using chron­ic and acute cal­ci­um manip­u­la­tions, causal­ly and bidi­rec­tion­al­ly link astro­cyte-cal­ci­um lev­els with fear expres­sion. In vivo cel­lu­lar-res­o­lu­tion cal­ci­um imag­ing revealed how neu­ronal rep­re­sen­ta­tions of fear are shaped by astro­cytes. Our find­ings reveal that retrieval of fear mem­o­ry involves a pre­vi­ous­ly unknown degree of func­tion­al inter­ac­tion between BA astro­cytes and neu­rons, redefin­ing cur­rent neu­ro­cir­cuit mod­els of an essen­tial sur­vival function.

Biog­ra­phy

Andrew Holmes spe­cial­iz­ing in neu­ro­science, with a focus on behav­ior and addic­tion. He was trained in the UK, where received his Bachelor’s (Hons) degree in Psy­chol­o­gy and his Doc­tor­ate in Behav­ioral Phar­ma­col­o­gy. He received post­doc­tor­al train­ing in behav­ioral neu­ro­science and behav­ioral genet­ics from Dr. Jac­ki Craw­ley at the NIMH. He was recruit­ed to the NIAAA in 2004 and is Cur­rent­ly lead­ing the Lab­o­ra­to­ry of Behav­ioral and Genom­ic Neu­ro­science at the Nation­al Insti­tute on Alco­hol Abuse and Alco­holism (NIAAA), part of the Nation­al Insti­tutes of Health (NIH), where he stud­ies brain reg­u­la­tion of emo­tion and cog­ni­tion using ani­mal models.

He obtained numer­ous awards, includ­ing in 2022 the NIAAA Sci­en­tif­ic Achieve­ment Award for ‘sci­en­tists who have made an out­stand­ing con­tri­bu­tion to sci­en­tif­ic research.’.

Research Top­ics

The mis­sion of the Lab­o­ra­to­ry of Behav­ioral and Genom­ic Neu­ro­science is to con­tribute to a deep­er under­stand­ing of the caus­es of alco­holism and comor­bid neu­ropsy­chi­atric con­di­tions such as mood and anx­i­ety dis­or­ders. Our goal is to help iden­ti­fy new direc­tions for the pre­ven­tion and effec­tive treat­ment of these dev­as­tat­ing dis­eases. To this end, we are using mod­els of chron­ic alco­hol expo­sure and chron­ic stress to exam­ine how these envi­ron­men­tal insults reshape brain cir­cuits to mod­i­fy behav­ior, and why they do so in a man­ner that varies great­ly from indi­vid­ual to indi­vid­ual as a func­tion of genet­ics, sex and age. A major cur­rent focus of our work is how alco­hol and stress affect the struc­ture and func­tion of cir­cuits inter­con­nect­ing the pre­frontal cor­tex with lim­bic and dor­sal stri­atal regions that are crit­i­cal for the reg­u­la­tion of emo­tion, cog­ni­tion and exec­u­tive con­trol over drug-seeking.