Electrocortical high frequency activity and respiratory entrainment in 6-hydroxydopamine model of Parkinson’s disease

Abstract

Parkinson s disease is characterized by motor symptoms (akinesia, rigidity, etc.), which are associated with the degeneration of the dopaminergic neurons of the midbrain. In addition, olfactory impairment that usually develops before the detection of motor deficits, is detected in 90% of Parkinsonian patients. Recent studies in mammals, have shown that slow cortical potentials phase-lock with nasal respiration. In several cortical areas, gamma synchronization of the electrographic activity is also coupled to respiration, suggesting than nasal respiratory entrainment could have a role in the processing of olfactory information. In the present study, we evaluate the role of midbrain dopaminergic neurons, in the modulation of the electrocorticogram activity and its respiratory entrainment during wakefulness and sleep. For this purpose, we performed a unilateral lesion of dopaminergic neurons of the substantia nigra pars compacta of the rat, with 6-hydroxydopamine. An increase in beta (20-35 Hz) together with a decrease in gamma power (60-95 Hz) in the motor cortex ipsilateral to the lesion was observed during wakefulness. These results correlated with the degree of motor alterations and dopamine measured at the striatum. Moreover, we found a decline in gamma coherence between the ipsilateral olfactory bulb and motor cortex. Also, at the olfactory bulb we noticed an increase in respiratory-gamma cross-frequency coupling after the lesion, while at the motor cortex, a decrease in respiratory potential entrainment of gamma activity was observed. Interestingly, we did not observe any significant modification either during Non-REM or REM sleep. These waking dysrhythmias may play a role both in the anosmia and motor deficits present in Parkinson disease.