Ketamine-Induced Oscillations in the Motor Circuit of the Rat Basal Ganglia

Abstract

Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinson's disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion.We recorded local field potentials from motor cortex, caudate-putamen (CPU), substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN) in 20 awake rats before and after the administration of ketamine at three different subanesthetic doses (10, 25 and 50 mg/Kg), and saline as control condition. Motor behavior was semiautomatically quantified by custom-made software specifically developed for this setting.Ketamine induced coherent oscillations in low gamma (50 Hz), high gamma (80 Hz) and high frequency (HFO, 150 Hz) bands, with different behavior in the four structures studied. While oscillatory activity at these three peaks was widespread across all structures, interactions showed a different pattern for each frequency band. Imaginary coherence at 150 Hz was maximum between motor cortex and the different basal ganglia nuclei, while low gamma coherence connected motor cortex with CPU and high gamma coherence was more constrained to the basal ganglia nuclei. Power at three bands correlated with the motor activity of the animal, but only coherence values in the HFO and high gamma range correlated with movement. Interactions in the low gamma band did not show a direct relationship to movement.These results suggest that the motor effects of ketamine administration may be primarily mediated by the induction of coherent widespread high-frequency activity in the motor circuit of the basal ganglia, together with a frequency-specific pattern of connectivity among the structures analyzed.

Electroencephalographic coherence and cortical acetylcholine during ketamine-induced unconsciousness

“…9 The emergence and recovery processes were characterized by increased high gamma activity and coherence. Similar increases in high gamma power and coherence have been reported after subanaesthetic doses of ketamine in rats [29][30][31] and humans. 32 In addition, subanaesthetic ketamine in rats induces hyperlocomotion, [29][30][31] which has been attributed to increases in power and coherence in higher gamma frequencies in the basal ganglia motor circuit.…”

“…Similar increases in high gamma power and coherence have been reported after subanaesthetic doses of ketamine in rats [29][30][31] and humans. 32 In addition, subanaesthetic ketamine in rats induces hyperlocomotion, [29][30][31] which has been attributed to increases in power and coherence in higher gamma frequencies in the basal ganglia motor circuit. 31 However, our observation of increased cortical gamma activity and coherence in both the absence and the presence of hyperlocomotion (i.e.…”

“…32 In addition, subanaesthetic ketamine in rats induces hyperlocomotion, [29][30][31] which has been attributed to increases in power and coherence in higher gamma frequencies in the basal ganglia motor circuit. 31 However, our observation of increased cortical gamma activity and coherence in both the absence and the presence of hyperlocomotion (i.e. before and after RORR) suggests that these may be independent effects of ketamine.…”

A PK–PD model of ketamine-induced high-frequency oscillations

“…This period was identified based on video recordings and wide-band spectral features [29]. Ketamine and MK-801 are know to distribute unevenly across the brain [30, 31] which may influence the observed instantaneous HFO power [17] and frequency [19]. Therefore, before computing the HFO power, median spectrograms for each rat and treatment were obtained from all recording sites.…”

Observation of Distressed Conspecific as a Model of Emotional Trauma Generates Silent Synapses in the Prefrontal-Amygdala Pathway and Enhances Fear Learning, but Ketamine Abolishes those Effects

“…Conversely, correlated pre-and post-synaptic activity causes synaptic unsilencing (Durand et al, 1996;Isaac et al, 1995;Liao et al, 1995). Synchronization of neuronal activity is a plausible mechanism for the effects of ketamine, which induces glutamate outflow and gamma oscillations in human and rodent brain (Hong et al, 2010;Nicolas et al, 2011;Pinault, 2008). Such oscillations may override the specific activity pattern required for silent synapse formation, or unsilence already formed silent synapses.…”