Dopamine D3 Receptors Inhibit Hippocampal Gamma Oscillations by Disturbing CA3 Pyramidal Cell Firing Synchrony

Abstract

Cortical gamma oscillations are associated with cognitive processes and are altered in several neuropsychiatric conditions such as schizophrenia and Alzheimer’s disease. Since dopamine D3 receptors are possible targets in treatment of these conditions, it is of great importance to understand their role in modulation of gamma oscillations. The effect of D3 receptors on gamma oscillations and the underlying cellular mechanisms were investigated by extracellular local field potential and simultaneous intracellular sharp micro-electrode recordings in the CA3 region of the hippocampus in vitro. D3 receptors decreased the power and broadened the bandwidth of gamma oscillations induced by acetylcholine or kainate. Blockade of the D3 receptors resulted in faster synchronization of the oscillations, suggesting that endogenous dopamine in the hippocampus slows down the dynamics of gamma oscillations by activation of D3 receptors. Investigating the underlying cellular mechanisms for these effects showed that D3 receptor activation decreased the rate of action potentials (APs) during gamma oscillations and reduced the precision of the AP phase coupling to the gamma cycle in CA3 pyramidal cells. The results may offer an explanation how selective activation of D3 receptors may impair cognition and how, in converse, D3 antagonists may exert pro-cognitive and antipsychotic effects.

NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity

“…Local field potentials were recorded in Haas-type recording chamber using a EXB-EXT-02B NPI Electronic amplifier (Norbert Polder Instruments, Germany), high-pass filtered at 0.1 Hz, low-pass filtered at 1 kHz and sampled at 5 kHz by a digitizer CED Micro1401-2 with a ADC12 extension (Cambridge Electronic Design Limited, Cambridge, UK) 71 . Gamma oscillations were induced by adding Cch (5 µM) to the perfusion after 1000 s baseline and recorded from the CA3 pyramidal layer with glass pipettes filled with aCSF (<4 MΩ).…”

The dopamine D3 receptor, a quarter century later

“…). The improvement of cognitive deficits induced by scopolamine appears to implicate the blockade of dopamine‐induced inhibition of gamma oscillations in the hippocampus (Lemercier et al ., ).…”

<p>Negative Symptoms in Schizophrenia: A Review and Clinical Guide for Recognition, Assessment, and Treatment</p>

“…46,47 This normalization of dopamine release in the prefrontal cortex could result in increased activation of D 1 receptors, which in turn could mediate improvements in cognition and negative symptoms. 47 D 3 receptors have also been associated with increased acetylcholine release in the prefrontal cortex, 41 regulation of glutamatergic excitability in the prefrontal cortex, 48,49 and regulation of dopamine, CREB phosphorylation, 50 and gamma oscillations 51 in the hippocampus, all mechanisms that could potentially contribute to the modulation of cognition and/or mood symptoms associated with schizophrenia. As such, D 3 antagonists and partial agonists may provide benefits in negative or cognitive symptoms.…”