{"id":231830,"date":"2026-02-21T21:12:34","date_gmt":"2026-02-22T03:12:34","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2026\/02\/astrocytes-enable-amygdala-neural-representations-supporting-memory"},"modified":"2026-02-21T21:12:34","modified_gmt":"2026-02-22T03:12:34","slug":"astrocytes-enable-amygdala-neural-representations-supporting-memory","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2026\/02\/astrocytes-enable-amygdala-neural-representations-supporting-memory","title":{"rendered":"Astrocytes enable amygdala neural representations supporting memory"},"content":{"rendered":"

<\/a><\/p>\n

A thorough study exploring how astrocytes affect fear conditioning and fear extinction in the basolateral amygdala of mice. Subpopulations of astrocytes were found to interact with neurons in such a way as to help encode representations of fear. [ https:\/\/www.nature.com\/articles\/s41586-025-10068-0<\/a>](https:\/\/www.nature.com\/articles\/s41586-025-10068-0<\/a>) <\/p>\n

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Gq<\/sub> G-protein-coupled receptor (GPCR) signalling increases astrocyte Ca2+<\/sup> activity through IP3-mediated release of intracellular Ca2+<\/sup> stores42<\/a>,43<\/a><\/sup> and hM3Dq actuation causes a Ca2+<\/sup> surge preceded by prolonged quiescence, possibly due to intracellular Ca2+<\/sup> depletion24<\/a>,44<\/a>,45<\/a><\/sup>. Replicating these effects in the BLA, we expressed hM3Dq in BLA astrocytes and used in vivo cyto-GCaMP6f photometry and observed that clozapine\u2013N<\/i>-oxide (CNO) injection markedly increased Ca2+<\/sup> activity within around 10 min but, thereafter, decreased and remained low for at least 2 h (Fig. 2c<\/a> and Extended Data Figs. 6a\u2013e<\/a> and 8e, f<\/a>). A lower hM3Dq virus concentration or lower CNO dose had modest or negligible effects on Ca2+<\/sup> activity and behaviour (Extended Data Fig. 6h\u2013p<\/a>). On the basis of these data, we posited that BLA astrocyte Ca2+<\/sup> dynamics would be constrained by hM3Dq actuation at timepoints relevant to behavioural testing. Consistent with this supposition, hM3Dq-actuation essentially abolished Ca2+<\/sup> responses to a potent stimulus (footshock) given 30 min after CNO injection (Extended Data Fig. 6f, g<\/a>).<\/p>\n

We leveraged these effects of hM3Dq actuation to test how constraining astrocyte Ca2+<\/sup> dynamics affected memory acquisition, retrieval, consolidation and extinction by injecting separate groups of animals with 3 mg per kg CNO either before or immediately after F-Con, or before fear retrieval\/extinction training. We found that CNO given before extinction training reduced CS-related freezing during E-Ext\u2014consistent with impaired memory retrieval\u2014in hM3Dq-expressing mice compared with viral controls (Fig. 2d, e<\/a>). In vivo fibre photometry confirmed that this behavioural effect was accompanied by loss of CS-related astrocyte Ca2+<\/sup> responses (Fig. 2f<\/a> and Extended Data Fig. 7a\u2013c<\/a>). In contrast to these memory-retrieval-impairing effects, CNO had no behavioural effect when injected before or after F-Con26<\/a>,27<\/a><\/sup> and did not alter uncued freezing, shock-induced flinching or various measures of anxiety-like behaviour (Extended Data Fig. 7d\u2013i<\/a>). Behavioural effects were also absent when CNO was injected in mice not expressing hM3Dq or when vehicle was injected in hM3Dq-expressing animals, excluding potential non-specific CNO and hM3Dq-virus effects, respectively (Extended Data Fig. 7j\u2013n<\/a>).<\/p>\n

We next compared these effects with those of another DREADD, hM4Di, that produces effects on cortical, striatal and (as we show here; Fig. 2g\u2013i<\/a>) BLA astrocyte Ca2+<\/sup> activity that mirror those of hM3Dq, that is, increase Ca2+<\/sup> transients24<\/a>,46<\/a>,47<\/a><\/sup>. Accordingly, we found that hM4Di actuation produced effects on memory retrieval that were opposite to hM3Dq: pre-Ext CNO injection produced increases in CS-related freezing and astrocyte Ca2+<\/sup> responses during E-Ext in hM4Di-expressing mice compared with viral controls (Fig. 2j\u2013l<\/a> and Extended Data Fig. 8a\u2013f<\/a>). Pre-Ext hM4Di actuation also increased freezing during (CNO-free) E-Ret, indicative of a deficit in extinction memory formation, and attenuated CS-related Ca2+<\/sup> activity during this test stage. This latter effect is notable given that hM3Dq actuation produced a similar extinction deficit and blunted the CS-related Ca2+<\/sup> response on E-Ret (Fig. 2e<\/a> and Extended Data Fig. 7b<\/a>), despite the two manipulations having opposite effects on fear retrieval and neither affecting extinction memory when CNO was given before E-Ret (Extended Data Fig. 8g, h<\/a>). This convergence of extinction-impairing effects suggests that extinction is sensitive to perturbations\u2014whether increases or decreases\u2014in astrocyte Ca2+<\/sup> activity and, by extension, implies an important role for BLA astrocytes in the plastic adaptations underlying extinction memory formation.<\/p>\n","protected":false},"excerpt":{"rendered":"

A thorough study exploring how astrocytes affect fear conditioning and fear extinction in the basolateral amygdala of mice. Subpopulations of astrocytes were found to interact with neurons in such a way as to help encode representations of fear. [ https:\/\/www.nature.com\/articles\/s41586-025-10068-0](https:\/\/www.nature.com\/articles\/s41586-025-10068-0) Gq G-protein-coupled receptor (GPCR) signalling increases astrocyte Ca2+ activity through IP3-mediated release of intracellular Ca2+ [\u2026]<\/p>\n","protected":false},"author":636,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,12,47],"tags":[],"class_list":["post-231830","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-existential-risks","category-neuroscience"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/231830","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/636"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=231830"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/231830\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=231830"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=231830"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=231830"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}