Dopamine acting at D1-like, D2-like and α1-adrenergic receptors differentially modulates theta and gamma oscillatory activity in primary motor cortex

Abstract

The loss of dopamine (DA) in Parkinson’s is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology. Recording local field potentials in deep layer V of rat M1, co-application of carbachol (CCh, 5 μM) and kainic acid (KA, 150 nM) elicited simultaneous oscillations at a frequency of 6.49 ± 0.18 Hz (theta, n = 84) and 34.97 ± 0.39 Hz (gamma, n = 84). Bath application of DA resulted in a decrease in gamma power with no change in theta power. However, application of either the D1-like receptor agonist SKF38393 or the D2-like agonist quinpirole increased the power of both theta and gamma suggesting that the DA-mediated inhibition of oscillatory power is by action at other sites other than classical DA receptors. Application of amphetamine, which promotes endogenous amine neurotransmitter release, or the adrenergic α1-selective agonist phenylephrine mimicked the action of DA and reduced gamma power, a result unaffected by prior co-application of D1 and D2 receptor antagonists SCH23390 and sulpiride. Finally, application of the α1-adrenergic receptor antagonist prazosin blocked the action of DA on gamma power suggestive of interaction between α1 and DA receptors. These results show that DA mediates complex actions acting at dopamine D1-like and D2-like receptors, α1 adrenergic receptors and possibly DA/α1 heteromultimeric receptors to differentially modulate theta and gamma activity in M1.

Ten-Hour Exposure to Low-Dose Ketamine Enhances Corticostriatal Cross-Frequency Coupling and Hippocampal Broad-Band Gamma Oscillations

“…Increased principal neuron activity and glutamate may increase gamma through the activation of metabotropic glutamate receptors ( Whittington et al, 1995 ). Finally, dopamine D1Rs may be involved in gamma generation in M1 ( Özkan et al, 2017 ). Ketamine-initiated gamma may also involve D1Rs as we observed that ketamine-induced locomotion and gamma in M1 were eliminated when ketamine was delivered after delivery of a D1R antagonist ( Figure 8 ).…”

Forelimb Motor Skills Deficits Following Thoracic Spinal Cord Injury: Underlying Dopaminergic and Neural Oscillatory Changes in Rat Primary Motor Cortex

“…Disruption of DA transmission in M1 occurs by various neurodegenerative disorders such as PD, multiple sclerosis, and TBI ( Gaspar et al, 1991 ). According to pre-clinical and clinical findings of PD studies, the reduction of DAergic projections from VTA to M1 is accompanied by the appearance of exaggerated spectral power of theta, beta, and gamma frequency bands in M1( Nimmrich et al, 2015 ; Ozkan et al, 2017 ; Wang et al, 2015 ). In line with these studies, our findings showed that, the reduction of D 1 R and D 2 R levels in FLA and HLA is correlated with increased LFP power after SCI.…”

“…The negative correlation of LFP power with the simultaneous decrease of D 1 R and D 2 R expressions may reflect the synergistic effects of both receptors on the modulation of M1 neural activity ( Awenowicz & Porter, 2002 ). These effects may be mediated directly via the expression of D 2 R in glutamatergic pyramidal neurons or indirectly through an expression of D 1 Rs on GABAergic interneurons ( Ozkan et al, 2017 ; Vitrac et al, 2014 ). It is noteworthy that the current study was designed to assess the effect of SCI on oscillatory activity and the DAergic system of M1, rather than to determine the underlying mechanism of their interactions.…”

“…Previous studies have shown that, the intact DA signaling in M1 is an essential component for the acquisition and storage of new motor skills at the cellular and synaptic levels ( Hosp & Luft, 2013 ; Ozkan et al, 2017 ). Confirming these theoretical notions, we found that deficit in motor skills learning following SCI is correlated with the reduced expression of D 1 R and D 2 R in Cont-FLA.…”

“…Therefore, it is hypothesized that reorganization in FLA after thoracic SCI could have a negative impact on related motor skills learning. Dopaminergic (DAergic) projections from the ventral tegmental area (VTA) to M1 play an essential role in M1 oscillatory activity ( Ozkan et al, 2017 ) and are required for successful motor skills learning ( Hosp & Luft, 2013 ). Interestingly, altered dopamine (DA) concentration in Parkinson disease (PD) and traumatic brain injury (TBI) is associated with alternation in M1 oscillatory activity, and motor skills deficit ( Gaspar et al, 1991 ; Pearson-Fuhrhop et al, 2013 ).…”