Dopamine D1 and D4 Receptor Subtypes Differentially Modulate Recurrent Excitatory Synapses in Prefrontal Cortical Pyramidal Neurons

Abstract

Although dopamine (DA) effects in the prefrontal cortex (PFC) have been studied extensively, the function of steady-state ambient levels of DA in the regulation of afferent excitatory transmission in PFC pyramidal neurons remains relatively unexplored. Using intracellular sharp-electrode and whole-cell recordings combined with intracellular labeling in brain slices, we found that D1/D5 receptor blockade did not alter synaptic responses in the PFC, but D1/D5 receptor activation consistently enhanced recurrent synaptic excitation in the majority of pyramidal neurons tested. In contrast, D4 receptor blockade resulted in an evoked complex multiple spike discharge pattern that contained both early and late (presumably multisynaptic) components of the evoked response that is contingent upon the preservation of axon collaterals of the neuron under study. Moreover, GABAergic interneurons were found to play a role in both responses; blockade of GABA a -mediated inhibition caused bath application of DA to convert monosynaptic excitatory postsynaptic potentials (EPSPs) to complex spike bursts riding on the late component of the EPSP. On the other hand, during the blockade of GABA amediated conductances, administration of a D4 receptor antagonist failed to facilitate evoked multiple spike discharge. Morphological analysis of axon collaterals of labeled neurons revealed that neurons in which the D4 receptor blockade induced the putative polysynaptic response had axon collaterals that were largely preserved. These data suggest that DA exerts a bidirectional modulation of PFC pyramidal neurons in brain slices provided that local network connections with interneurons are preserved, with D4 receptors under tonic stimulation by ambient low levels of DA, whereas D1/D5 receptors activated upon phasic DA input.

Dopamine D1versus D4Receptors Differentially Modulate the Encoding of Salient versus Nonsalient Emotional Information in the Medial Prefrontal Cortex

“…Disturbances in these processes may lead to the formation of inappropriately reinforced associative memories, maladaptive behaviors, and delusional ideation, all of which are typically present in schizophrenia-related psychoses. Within the medial prefrontal cortex (mPFC), cognitive, emotional, and motivational processes are strongly modulated by dopamine (DA) transmission and, in particular, through signaling via the DA D 1 and the D 4 receptor subtypes (Seamans et al, 1998;Pezze et al, 2003;Laviolette et al, 2005;Onn et al, 2006). Dopaminergic modulation of mPFC neuronal networks is known to control the encoding of working memory and the temporal sequencing of behavioral output (Goldman-Rakic et al, 1989;Goldman-Rakic, 1995;Seamans et al, 1998).…”

High frequency stimulation-induced plasticity in the prelimbic cortex of rats emerges during adolescent development and is associated with an increase in dopamine receptor function

“…To test this hypothesis, we examined the effect of D1 and D2/D4 agonists on the field potential in the adolescent and adult mPFC. These receptors have been suggested to play an important role in modulating both interneuron and pyramidal cell activity (Onn et al, 2006;Zhong and Yan, 2016) and their affinity to respective agonist increases during adolescence (Tarazi and Baldessarini, 2000). Moreover, we chose quinpirole to stimulate D2/D4 receptors so our results could be compared directly to several early findings showing developmental changes in the effect of this drug on evoked EPSP (Tseng and O'Donnell, 2007b) and interneuron excitability (Tseng and O'Donnell, 2007a) in the mPFC.…”

Dopamine and cyclic-AMP regulated phosphoprotein-32–dependent modulation of prefrontal cortical input and intercellular coupling in mouse accumbens spiny and aspiny neurons

“…Also excluded were neurons with unstable membrane potentials or access resistance (>10% changes) before drug application. During whole cell recordings, biocytin readily diffused from the patch recording pipette into the recorded neuron and was processed histochemically post hoc for cell location and morphology (Onn et al, 2006a). …”

“…The biocytin-filled microelectrodes were lowered into the accumbens core region under visual control using a stereomicroscope (Nikon SMZ-2B; Melville, NY) by reference to anatomical landmarks on a mouse brain atlas. After impalement of a cell with stable membrane potentials, cells were injected with biocytin using 0.5-1 nA depolarizing current pulses delivered at 3.3 Hz (Onn et al, 2003(Onn et al, , 2006a …”

“…After impalement of a cell with stable membrane potentials, cells were injected with biocytin using 0.5-1 nA depolarizing current pulses delivered at 3.3 Hz (Onn et al, 2003(Onn et al, , 2006a …”