In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 33, No. 34 ( 2013-08-21), p. 13583-13599
Abstract:
In many cortical neurons, HCN1 channels are the major contributors to I h , the hyperpolarization-activated current, which regulates the intrinsic properties of neurons and shapes their integration of synaptic inputs, paces rhythmic activity, and regulates synaptic plasticity. Here, we examine the physiological role of I h in deep layer pyramidal neurons in mouse prefrontal cortex (PFC), focusing on persistent activity, a form of sustained firing thought to be important for the behavioral function of the PFC during working memory tasks. We find that HCN1 contributes to the intrinsic persistent firing that is induced by a brief depolarizing current stimulus in the presence of muscarinic agonists. Deletion of HCN1 or acute pharmacological blockade of I h decreases the fraction of neurons capable of generating persistent firing. The reduction in persistent firing is caused by the membrane hyperpolarization that results from the deletion of HCN1 or I h blockade, rather than a specific role of the hyperpolarization-activated current in generating persistent activity. In vivo recordings show that deletion of HCN1 has no effect on up states, periods of enhanced synaptic network activity. Parallel behavioral studies demonstrate that HCN1 contributes to the PFC-dependent resolution of proactive interference during working memory. These results thus provide genetic evidence demonstrating the importance of HCN1 to intrinsic persistent firing and the behavioral output of the PFC. The causal role of intrinsic persistent firing in PFC-mediated behavior remains an open question.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.2427-12.2013
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2013
detail.hit.zdb_id:
1475274-8
SSG:
12
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