Article

Plasticity of Prefrontal Attention Circuitry: Upregulated Muscarinic Excitability in Response to Decreased Nicotinic Signaling Following Deletion of 5 or 2 Subunits

Department of Physiology, University of Toronto, Toronto, Ontario M5S1A8, Canada.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 11/2011; 31(45):16458-63. DOI: 10.1523/JNEUROSCI.3600-11.2011
Source: PubMed

ABSTRACT Attention depends on cholinergic stimulation of nicotinic and muscarinic acetylcholine receptors in the medial prefrontal cortex. Pyramidal neurons in layer VI of this region express cholinergic receptors of both families and play an important role in attention through their feedback projections to the thalamus. Here, we investigate how nicotinic and muscarinic cholinergic receptors affect the excitability of these neurons using whole-cell recordings in acute brain slices of prefrontal cortex. Since attention deficits have been documented in both rodents and humans having genetic abnormalities in nicotinic receptors, we focus in particular on how the cholinergic excitation of layer VI neurons is altered by genetic deletion of either of two key nicotinic receptor subunits, the accessory α5 subunit or the ligand-binding β2 subunit. We find that the cholinergic excitation of layer VI neurons is dominated by nicotinic receptors in wild-type mice and that the reduction or loss of this nicotinic stimulation is accompanied by a surprising degree of plasticity in excitatory muscarinic receptors. These findings suggest that disrupting nicotinic receptors fundamentally alters the mechanisms and timing of excitation in prefrontal attentional circuitry.

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    • "In addition, knocking out genes can induce compensatory effects and developmental changes. Indeed, it is known that mice lacking β2 subunits have an upregulation of muscarinic excitability (Tian et al., 2011). Interestingly, it has also been demonstrated that the α5 subunit , which is present on layer VI pyramidal neurons, is necessary for normal attention behavior (Bailey et al., 2010). "
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