Acute nicotine exposure produces a spatially organized transcriptional response in mouse olfactory cortex

Nicotine acts on nicotinic receptors throughout the forebrain. Most molecular studies of its effects, however, have focused on reward circuitry and have used bulk tissue, which cannot show which cells respond or how responding cells are arranged relative to one another. We previously found that a single nicotine exposure activates hippocampal astrocytes through the astrocyte-expressed kinase AKT2. Here we asked which cells respond to nicotine in the anterior olfactory cortex, a cholinergic-modulated region that encodes odor associations, and whether their astrocytic surroundings change. Male mice received a single intraperitoneal injection of nicotine or saline, and coronal sections spanning the anterior olfactory nucleus, piriform cortex and adjacent isocortex were sequencing 24 h later using Visium HD. Differential expression on nucleus-based segmentation was concentrated in olfactory excitatory neurons. Pathways centered on calcium-handling, synapse-assembly and extracellular-matrix programs, together with a lasting reduction of the immediate-early gene Egr1. Within the piriform region, the response localized to a continuous population of superficial pyramidal neurons expressing Cartpt and Penk. These neurons upregulated synapse-assembly, receptor-regulation and proteoglycan programs without changes to cell-type proportions. Nicotine also reduced expression of Sparcl1, which encodes astrocyte-secreted synaptogenic protein hevin, within one cell diameter of these neurons. Our study shows that a single nicotine exposure leaves a spatially organized transcriptional program on olfactory circuitry, centered on one neuronal population and the tissue at its border. These results identify candidate cells, genes and tissue locations for testing how nicotine alters sensory cue circuits.

Griffioen, M. K., Lombardi, A., Milstead, R., Borski, C., Zou, S., Stitzel, J., Ehringer, M. A., Hoeffer, C. A.

Stats

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.