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Publication : α4* Nicotinic acetylcholine receptors modulate experience-based cortical depression in the adult mouse somatosensory cortex.

First Author  Brown CE Year  2012
Journal  J Neurosci Volume  32
Issue  4 Pages  1207-19
PubMed ID  22279206 Mgi Jnum  J:180586
Mgi Id  MGI:5306678 Doi  10.1523/JNEUROSCI.4568-11.2012
Citation  Brown CE, et al. (2012) alpha4* Nicotinic Acetylcholine Receptors Modulate Experience-Based Cortical Depression in the Adult Mouse Somatosensory Cortex. J Neurosci 32(4):1207-19
abstractText  The molecular mechanisms that mediate experience-based changes in the function of the cerebral cortex, particularly in the adult animal, are poorly understood. Here we show using in vivo voltage-sensitive dye imaging, that whisker trimming leads to depression of whisker-evoked sensory responses in primary, secondary and associative somatosensory cortical regions. Given the importance of cholinergic neurotransmission in cognitive and sensory functions, we examined whether alpha4-containing (alpha4*) nicotinic acetylcholine receptors (nAChRs) mediate cortical depression. Using knock-in mice that express YFP-tagged alpha4 nAChRs subunits, we show that whisker trimming selectively increased the number alpha4*-YFP nAChRs in layer 4 of deprived barrel columns within 24 h, which persisted until whiskers regrew. Confocal and electron microscopy revealed that these receptors were preferentially increased on the cell bodies of GABAergic neurons. To directly link these receptors with functional cortical depression, we show that depression could be induced in normal mice by topical application or micro-injection of alpha4* nAChR agonist in the somatosensory cortex. Furthermore, cortical depression could be blocked after whisker trimming with chronic infusions of an alpha4* nAChR antagonist. Collectively, these results uncover a new role for alpha4* nAChRs in regulating rapid changes in the functional responsiveness of the adult somatosensory cortex.
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