Basal Forebrain and Brainstem Cholinergic Neurons Differentially Impact Amygdala Circuits and Learning-Related Behavior
MetadataShow full item record
Aitta-aho, T., Hay, A., Phillips, B., Saksida, L., Bussey, T., Paulsen, O., & Apergis-Schoute, J. (2018). Basal Forebrain and Brainstem Cholinergic Neurons Differentially Impact Amygdala Circuits and Learning-Related Behavior. Current Biology, 28 (16), 2557-2569.e4. https://doi.org/10.1016/j.cub.2018.06.064
The central cholinergic system and the amygdala are well-known to be important for motivation and mnemonic processes. Different cholinergic populations innervate the amygdala but it is unclear how these projections impact amygdala activity and behavior. 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. Photoactivating 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 NBm-ChAT inputs to the basal nucleus resulted in endogenous ACh release resulting in muscarinic receptor dependent biphasic inhibition-excitation responses onto principal neurons. Such a biphasic inhibitory-excitatory response profile is a physiological hallmark 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. Stimulation-evoked and ongoing increases in gamma and theta power were dependent on local nicotinic or muscarinic receptor activation, respectively. Activation of brainstem ChAT-containing neurons however resulted in a transient increase in central lateral amygdala network synchrony 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 amygdala-dependent memories.
This work was supported by the Royal Society, The Wellcome Trust (JAS), the Sigrid Juselius Foundation (TA), and by a Herchel Smith Fellowship (YAH).
External DOI: https://doi.org/10.1016/j.cub.2018.06.064
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279734