The Mechanistic Study Of DOM On Gamma Oscillations In Thalamic Cortical Network

The thalamic reticular nucleus（TRN）is an organized and complex population of GABAergic neurons distributed with 5-HT_2A receptors that provides strict regulation of the information processing between thalamus and cerebral cortex.Gamma oscillations（30-80Hz）are involved in a variety of cognitive functions,such as attentional selection and sensory stimulation.Gamma oscillations are mainly mediated by PV interneurons.The 40 Hz gamma oscillations originates from the TRN and is closely related to sensory information integration in the thalamocortical pathway.Hallucinogen produces change in perception,thought,feeling and positive psychotic symptoms similar to those of schizophrenics,such as hallucinations and delusions.Hallucination and abnormal 40 Hz gamma oscillations are also associated with some degenerative neurological diseases.Currently,the underlying mechanisms have been less well investigated.Hallucinogen is likely to affect the integration and synchronization of perception information in the thalamocortical pathway that produce hallucination in the brain.The abuse of psychedelic drugs such as 2,5-dimethoxy methylopropylamine（DOM）can also cause criminal offences and adverse social effects.Therefore,DOM is used as a drug model and combined with the accepted head twitch response（HTR）for the evaluation of hallucinogens in this study to find the neural mechanism of its action.There are two aspects of this study,（1）Effects of hallucinogens DOM on 40 Hz gamma oscillations in thalamocortical networks.Gamma oscillations were recorded in mice TRN and verified by means of the GABA_A receptor antagonist bicuculline and T-type calcium channel antagonist TTA-A2.The results are consistent with the references.The power spectrum of gamma oscillations were reduced by bicuculline（0.3 mg/kg）and TTA-A2（1mg/kg）,indicating that gamma oscillations were recorded successfully.Based on the effects DOM on 5-HT_2A receptor,we found that 5-hydroxytryptophan（75 mg/kg）,the precursor of5-HT,increased the gamma oscillations power spectrum in TRN of mice.While the non-hallucinogenic 5-HT_2A receptor agonist,lisuride,had no significant effect on the gamma oscillations power spectrum.DOM decreased the power spectrum of 40 Hz gamma oscillations in the TRN,and 5-HT_2A receptor antagonist MDL100907 partially reversed the effects of DOM.This suggests that DOM affected 40 Hz gamma oscillations in the thalamocortical pathway.（2）40 Hz optical activates PV interneurons in TRN and glutamatergic inputs from the cingulate cortex（Cg）upstream of TRN to influence the behavior of DOM induced HTR.It was found that 40 Hz optical activated PV interneurons in TRN and glutamatergic inputs from the Cg upstream of TRN to reduce the number of HTR induced by DOM,while 20 Hz and 80 Hz optical activation had no significant effect.These results suggest that the 40 Hz gamma oscillations of the thalamocortical network may be involved in the HTR induced by DOM.This study may provide a theoretical basis for the neural mechanism of hallucinations.