Late Adolescent Expression of GluN2B Transmission in the Prefrontal Cortex Is Input-Specific and Requires Postsynaptic Protein Kinase A and D1 Dopamine Receptor Signaling

doi:10.1016/j.biopsych.2013.07.033

Biological Psychiatry

Volume 75, Issue 6, 15 March 2014, Pages 508-516

https://doi.org/10.1016/j.biopsych.2013.07.033 Get rights and content

Background

Refinement of mature cognitive functions, such as working memory and decision making, typically takes place during adolescence. The acquisition of these functions is linked to the protracted development of the prefrontal cortex (PFC) and dopamine facilitation of glutamatergic transmission. However, the mechanisms that support these changes during adolescence remain elusive.

Methods

Electrophysiological recordings (in vitro and in vivo) combined with pharmacologic manipulations were employed to determine how N-methyl-D-aspartate transmission in the medial PFC changes during the adolescent transition to adulthood. The relative contribution of GluN2B transmission and its modulation by postsynaptic protein kinase A and D1 receptor signaling were determined in two distinct age groups of rats: postnatal day (P)25 to P40 and P50 to P80.

Results

We found that only N-methyl-D-aspartate receptor transmission onto the apical dendrite of layer V pyramidal neurons undergoes late adolescent remodeling due to a functional emergence of GluN2B function after P40. Both protein kinase A and dopamine D1 receptor signaling are required for the functional expression of GluN2B transmission and to sustain PFC plasticity in response to ventral hippocampal, but not basolateral amygdala, inputs.

Conclusions

Thus, the late adolescent acquisition of GluN2B function provides a mechanism for dopamine D1-mediated regulation of PFC responses in an input-specific manner.

Section snippets

Methods and Materials

All experimental procedures were approved by the Rosalind Franklin University Institutional Animal Care and Use Committee according to the U.S. Public Health Service Guide for Care and Use of Laboratory Animals. Male Sprague-Dawley rats (Harlan, Indianapolis, Indiana) from P25 to P85 were allowed to acclimate to the animal facility for at least 5 days before being used, group-housed (2 to 3 rats per cage) with food and water available ad libitum, and maintained at 21°C to 23°C in a 12-hour

Results

We first examined whether glutamatergic transmission onto the apical dendrite of layer V medial PFC pyramidal neurons is developmentally regulated during the transition from juvenile/early adolescence (P25–P40) to late adolescence/adulthood (P50–P80). Analyses of the evoked response revealed that both age groups exhibit similar EPSC amplitude at the −70 mV (EPSC_−70mV) and at the +60 mV (EPSC_+60mV) holding potentials (Figure 1A). Similarly, the EPSC_−70mV duration was indistinguishable among

Discussion

In the present study, we found that NMDA-mediated transmission onto the apical dendrite of layer V pyramidal neurons in the medial PFC undergoes a specific developmental upregulation during the adolescent transition to adulthood. Both postsynaptic PKA signaling and local prefrontal D1 receptor tone are necessary, but not sufficient, to sustain the characteristic long-lasting NMDA response that begins to emerge ~P45 (Figure 8A,B). Our results also indicate that such developmental facilitation is

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Archival ReportLate Adolescent Expression of GluN2B Transmission in the Prefrontal Cortex Is Input-Specific and Requires Postsynaptic Protein Kinase A and D1 Dopamine Receptor Signaling

Background

Methods

Results

Conclusions

Section snippets

Methods and Materials

Results

Discussion

Biol Psychiatry

Biol Psychiatry

Neuron

Prog Neurobiol

Neuropharmacology

Neuron

Neuropharmacology

Neuron

Neuroscience

Neuron

Neurobiol Aging

Brain Res

Brain Res

Neuropsychologia

Pharmacol Biochem Behav

A developmental perspective on executive function

Child Dev

Maturation of cognitive processes from late childhood to adulthood

Child Dev

Convergence and interaction of hippocampal and amygdalar projections within the prefrontal cortex in the rat

J Neurosci

Post-pubertal emergence of prefrontal cortical up states induced by D1-NMDA co-activation

Cereb Cortex

Parallel maturation of goal-directed behavior and dopaminergic systems during adolescence

J Neurosci

Appetitive instrumental learning requires coincident activation of NMDA and dopamine D1 receptors within the medial prefrontal cortex

J Neurosci

Essential role of D1 but not D2 receptors in the NMDA receptor-dependent long-term potentiation at hippocampal-prefrontal cortex synapses in vivo

J Neurosci

Blockade of NMDA GluN2B receptors selectively impairs behavioral flexibility but not initial discrimination learning

Psychopharmacology (Berl)

Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex

Learn Mem

Archival Report
Late Adolescent Expression of GluN2B Transmission in the Prefrontal Cortex Is Input-Specific and Requires Postsynaptic Protein Kinase A and D1 Dopamine Receptor Signaling