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bioRxiv · 10.1101/368134

Basal forebrain and brainstem cholinergic neurons differentially impact amygdala circuits and learning-related behavior

Aitta-aho, T.·Hay, Y. A.·Phillips, B. U.·Saksida, L. M.·Bussey, T. J.·Paulsen, O.·Apergis-Schoute, J.
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Abstract

The central cholinergic system and the amygdala are important for motivation and mnemonic processes. Different cholinergic populations innervate the amygdala but it is unclear how these projections impact amygdala processes. Using optogenetic circuit-mapping strategies in ChAT-cre mice we demonstrate that amygdala-projecting basal forebrain and brainstem ChAT-containing neurons can differentially affect amygdala circuits and behavior. Photo-activating ChAT terminals in vitro revealed the underlying synaptic impact of brainstem inputs to the central lateral division to be excitatory, mediated via the synergistic glutamatergic activation of AMPA and NMDA receptors. In contrast, stimulating basal forebrain inputs to the basal nucleus resulted in endogenous ACh release resulting in biphasic inhibition-excitation responses onto principal neurons. Such response profiles are physiological hallmarks of neural oscillations and could thus form the basis of acetylcholine-mediated rhythmicity in amygdala networks. Consistent with this, in vivo NBm activation strengthened amygdala basal nucleus theta and gamma frequency rhythmicity, both of which continued for seconds after stimulation and were dependent on local muscarinic or nicotinic receptor activation, respectively. Activation of brainstem ChAT-containing neurons however resulted in a transient increase in central lateral amygdala activity that was independent of cholinergic receptors. In addition, driving these respective inputs in behaving animals induced opposing appetitive and defensive learning-related behavioral changes. Since learning and memory is supported by both cellular and network-level processes in central cholinergic and amygdala networks, these results provide a route by which distinct cholinergic inputs can convey salient information to the amygdala and promote associative biophysical changes that underlie emotional memories.

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Aitta-aho, T., Hay, Y. A., Phillips, B. U., Saksida, L. M., Bussey, T. J., Paulsen, O., Apergis-Schoute, J.. 2018-07-12. Basal forebrain and brainstem cholinergic neurons differentially impact amygdala circuits and learning-related behavior. https://doi.org/10.1101/368134

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