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.
Highlights
The synchronization of neuronal activity may be mechanistically important for information processing across different levels of the sensory and motor systems [1], [2]
Abnormal synchronization has been found in other neurological diseases, such as Parkinson’s disease, where an exaggerated synchronization exists in the beta frequency band between the motor cortex and different basal ganglia nuclei, with changes to the gamma range after dopaminergic intake [4], [5], [6],[7]
After saline injection, the power spectra were similar in the four structures in relative terms, motor cortex presented the highest absolute values in power
Summary
The synchronization of neuronal activity may be mechanistically important for information processing across different levels of the sensory and motor systems [1], [2]. Altered oscillatory activity (suggesting the presence of abnormalities in neuronal synchronization) has been reported in schizophrenia, around the gamma range [3]. Ketamine is a pharmacological antagonist of NMDA glutamate receptors It can induce hallucinations and paranoia comparable with the positive symptoms of schizophrenia, and can cause behaviors similar to the negative symptoms of schizophrenia, like social withdrawal, poverty of speech and blunted affect [8]. Subanaesthetic doses have been described as producing hyperlocomotion, altered social interaction, sterotypies and impaired cognitive function. Some of these behaviors are similar to those observed in schizophrenic patients, suggesting that NMDA receptor hypofunction might contribute to some of the symptoms of schizophrenia [9]. It has been proposed that the hyper-locomotion observed might be the consequence of cognitive and perceptive disturbances mimicking the cognitive dysfunction observed in schizophrenic patients
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