Archival ReportStress Impairs Prefrontal Cortical Function via D1 Dopamine Receptor Interactions With Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Section snippets
Methods and Materials
All procedures were approved by the Yale Institutional Animal Care and Use Committee.
HCN Channels and D1Rs Colocalize in Dendritic Spines of Monkey DLPFC
Dual immunoelectron microscopy revealed coexpression of D1Rs and HCN channels in pyramidal neurons, as well as spatial interaction on spine membranes in layer III monkey DLPFC. Both proteins were localized in the synthetic machinery in the soma (Figure 3A) and colocalized at the plane of the plasma membrane of dendritic spines (Figure 3B–E). Although HCN channels are prominent along the distal pyramidal dendrites, D1Rs are not present at this location (26). Thus, colocalization was found in the
Discussion
The current study showed that the impairment in PFC function during stress involves D1R opening of HCN channels to weaken PFC network connections. Combining anatomical, physiological, and behavioral evidence, we found that 1) D1Rs and HCN channels colocalize and spatially interact at dendritic spines in monkey layer III DLPFC; 2) stimulation of D1Rs increases Ih in mouse PFC slices; 3) suppression of neuronal firing by D1R-cAMP signaling can be prevented by blocking HCN channels in monkey
Acknowledgments and Disclosures
This work was supported by National Institute of Neurological Disorders and Stroke NS07224 to NJG, Public Health Service RL1AA017536 to AFTA within Consortium U54RR024350, National Alliance for Research on Schizophrenia and Depression Young Investigator Grant to YY, and National Institute of Mental Health MH099045 and a Smith Family Award for Excellence in Biomedical Research to MJH.
We thank Lisa Ciavarella, Tracy Sadlon, Sam Johnson, Michelle Wilson, and Jessica Thomas Ebbett for their
References (84)
Cellular basis of working memory
Neuron
(1995)Circuitry of the frontal association cortex and its relevance to dementia
Arch Gerontol Geriatr
(1987)- et al.
NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex
Neuron
(2013) - et al.
Dynamic network connectivity: A new form of neuroplasticity
Trends Cogn Sci
(2010) - et al.
Functional heteromerization of HCN1 and HCN2 pacemaker channels
J Biol Chem
(2001) - et al.
Rodent models of prefrontal cortical function
Trends Neurosci
(2002) - et al.
Inactivation of the medial prefrontal cortex of the rat impairs strategy set-shifting, but not reversal learning, using a novel, automated procedure
Behav Brain Res
(2008) - et al.
Do rats have a prefrontal cortex?
Behav Brain Res
(2003) - et al.
Severe anxiety induced by FG 7142, a beta-carboline ligand for benzodiazepine receptors
Lancet
(1983) - et al.
Region-specific effects of acute and repeated restraint stress on the phosphorylation of mitogen-activated protein kinases
Brain Res
(2003)
A role for norepinephrine in stress-induced cognitive deficits: Alpha-1-adrenoceptor mediation in the prefrontal cortex
Biol Psychiatry
Postsynaptic cAMP pathway gates early LTP in hippocampal CA1 region
Neuron
6-Hydroxydopamine lesion of the rat prefrontal cortex increases locomotor activity, impairs acquisition of delayed alternation tasks, but does not affect uninterrupted tasks in the radial maze
Behav Brain Res
Activation of presynaptic D1 dopamine receptors by dopamine increases the frequency of spontaneous excitatory postsynaptic currents through protein kinase A and protein kinase C in pyramidal cells of rat prelimbic cortex
Neuroscience
Structural elements of instantaneous and slow gating in hyperpolarization-activated cyclic nucleotide-gated channels
J Biol Chem
Pacemaker channels produce an instantaneous current
J Biol Chem
A behavioral role for dendritic integration: HCN1 channels constrain spatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons
Cell
A novel mechanism of modulation of hyperpolarization-activated cyclic nucleotide-gated channels by Src kinase
J Biol Chem
Catecholamine and second messenger influences on prefrontal cortical networks of “representational knowledge”: A rational bridge between genetics and the symptoms of mental illness
Cereb Cortex
Stress signalling pathways that impair prefrontal cortex structure and function
Nat Rev Neurosci
Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance
J Neurosci
Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory
Nat Neurosci
D1 dopamine receptors in the mouse prefrontal cortex: Immunocytochemical and cognitive neuropharmacological analyses
Synapse
Dose-dependent effects of the dopamine D1 receptor agonists A77636 or SKF81297 on spatial working memory in aged monkeys
J Pharmacol Exp Ther
Estrogen shapes dopamine-dependent cognitive processes: Implications for women׳s health
J Neurosci
Additive effects of genetic variation in dopamine regulating genes on working memory cortical activity in human brain
J Neurosci
Neuroplasticity of neocortical circuits in schizophrenia
Neuropsychopharmacology
Increased prefrontal cortical D1 receptors in drug naive patients with schizophrenia: A PET study with [11C]NNC112
J Psychopharmacol
Stress and schizophrenia: Advances in neuropsychiatry and psychopharmacology
Intrinsic circuit organization of the major layers and sublayers of the dorsolateral prefrontal cortex in the rhesus monkey
J Comp Neurol
Isodirectional tuning of adjacent interneurons and pyramidal cells during working memory: Evidence for microcolumnar organization in PFC
J Neurophysiol
Functional synergism between putative gamma-aminobutyrate-containing neurons and pyramidal neurons in prefrontal cortex
Proc Natl Acad Sci U S A
Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys
Proc Natl Acad Sci U S A
Presynaptic regulation of recurrent excitation by D1 receptors in prefrontal circuits
Proc Natl Acad Sci U S A
Dopamine D1 receptor actions in layers V-VI rat prefrontal cortex neurons in vitro: Modulation of dendritic-somatic signal integration
J Neurosci
Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex
Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide
J Gen Physiol
Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain
J Comp Neurol
Constellation of HCN channels and cAMP regulating proteins in dendritic spines of the primate prefrontal cortex: Potential substrate for working memory deficits in schizophrenia
Cereb Cortex
Hyperpolarization-activated cation currents: From molecules to physiological function
Annu Rev Physiol
Projection-specific neuromodulation of medial prefrontal cortex neurons
J Neurosci
Do rats have prefrontal cortex? The Rose-Woolsey-Akert program reconsidered
J Cogn Neurosci
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