alpha2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex.

@article{citeulike:1255226, abstract = {Spatial working memory (WM; i.e., "scratchpad" memory) is constantly updated to guide behavior based on representational knowledge of spatial position. It is maintained by spatially tuned, recurrent excitation within networks of prefrontal cortical (PFC) neurons, evident during delay periods in WM tasks. Stimulation of postsynaptic alpha2A adrenoceptors (alpha2A-ARs) is critical for WM. We report that alpha2A-AR stimulation strengthens WM through inhibition of cAMP, closing Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels and strengthening the functional connectivity of PFC networks. Ultrastructurally, HCN channels and alpha2A-ARs were colocalized in dendritic spines in PFC. In electrophysiological studies, either alpha2A-AR stimulation, cAMP inhibition or HCN channel blockade enhanced spatially tuned delay-related firing of PFC neurons. Conversely, delay-related network firing collapsed under conditions of excessive cAMP. In behavioral studies, either blockade or knockdown of HCN1 channels in PFC improved WM performance. These data reveal a powerful mechanism for rapidly altering the strength of WM networks in PFC.}, address = {Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510 USA.}, author = {Wang, M. and Ramos, B. P. and Paspalas, C. D. and Shu, Y. and Simen, A. and Duque, A. and Vijayraghavan, S. and Brennan, A. and Dudley, A. and Nou, E. and Mazer, J. A. and McCormick, D. A. and Arnsten, A. F. }, citeulike-article-id = {1255226}, doi = {10.1016/j.cell.2007.03.015}, issn = {0092-8674}, journal = {Cell}, keywords = {hcn, h-current, pfc, working\_memory}, month = {April}, number = {2}, pages = {397--410}, posted-at = {2008-05-12 13:57:42}, priority = {4}, title = {alpha2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex.}, url = {http://dx.doi.org/10.1016/j.cell.2007.03.015}, volume = {129}, year = {2007} }

TY - JOUR ID - citeulike:1255226 L3 - citeulike-article-id:1255226 TI - alpha2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex. JF - Cell VL - 129 IS - 2 SP - 397 EP - 410 AD - Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510 USA. SN - 0092-8674 N2 - Spatial working memory (WM; i.e., "scratchpad" memory) is constantly updated to guide behavior based on representational knowledge of spatial position. It is maintained by spatially tuned, recurrent excitation within networks of prefrontal cortical (PFC) neurons, evident during delay periods in WM tasks. Stimulation of postsynaptic alpha2A adrenoceptors (alpha2A-ARs) is critical for WM. We report that alpha2A-AR stimulation strengthens WM through inhibition of cAMP, closing Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels and strengthening the functional connectivity of PFC networks. Ultrastructurally, HCN channels and alpha2A-ARs were colocalized in dendritic spines in PFC. In electrophysiological studies, either alpha2A-AR stimulation, cAMP inhibition or HCN channel blockade enhanced spatially tuned delay-related firing of PFC neurons. Conversely, delay-related network firing collapsed under conditions of excessive cAMP. In behavioral studies, either blockade or knockdown of HCN1 channels in PFC improved WM performance. These data reveal a powerful mechanism for rapidly altering the strength of WM networks in PFC. KW - hcn KW - h-current KW - pfc KW - working_memory AU - Wang, M AU - Ramos, BP AU - Paspalas, CD AU - Shu, Y AU - Simen, A AU - Duque, A AU - Vijayraghavan, S AU - Brennan, A AU - Dudley, A AU - Nou, E AU - Mazer, JA AU - McCormick, DA AU - Arnsten, AF PY - 2007/04/20/ UR - http://dx.doi.org/10.1016/j.cell.2007.03.015 ER -