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The role of muscarinic receptors in prefrontal excitability and fear extinction
Author(s) -
Santini Edwin,
Sepulveda-Orengo Marian T.,
Porter James T.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.709.4
Subject(s) - extinction (optical mineralogy) , neuroscience , muscarinic acetylcholine receptor , psychology , prefrontal cortex , fear conditioning , recall , agonist , infralimbic cortex , chemistry , receptor , medicine , cognitive psychology , cognition , amygdala , mineralogy
Fear extinction enhances the intrinsic excitability of infralimbic (IL) prefrontal neurons. We recently showed that IL excitability is modulated by M‐type K+ channels. Given that muscarinic receptors (MusRs) inhibit M‐channels, cholinergic inputs to IL may play a role in controlling IL excitability and fear extinction. To test this hypothesis, we combined patch‐clamp recordings and fear conditioning. In brain slices, muscarine increased the number of neuronal spikes by reducing the M‐current indicating that MusRs enhance the intrinsic excitability of IL neurons. Next, we showed that systemic injection and intra‐IL infusion of the MusRs antagonist, scopolamine, prior to extinction training impaired recall of extinction 24‐hrs later. Finally, systemic injections of the muscarinic agonist, cevimeline, facilitated recall of extinction. Together these findings suggest that cholinergic inputs to IL play an important role in consolidation of fear extinction and that muscarinic agonists might be useful to facilitate extinction memory in patients with anxiety disorders. Supported by NSF grant IOS 0842159 to JTP, RCMI Behavioral Core Facility 5G12RR003050‐26 and MBRS RISE 1R25GM082406 to MS.