Influence of the inferior colliculus on motor deficits of parkinsonian rodents: behavioral and electrophysiological studies

• Applicant: Dr. Liana Melo-Thomas, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; General, Cognitive and Mathematical Psychology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 308581546

The disease of Parkinson (PD) is a neurodegenerative disorder which is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Loss of SNc neurons leads to striatal dopamine (DA) deficiency, which is responsible for the major PD symptoms such as bradykinesia, resting tremor, muscle rigidity, and postural abnormalities. In respect to bradykinesia it has been suggested that severely disabled patients remain able to produce a sudden and brief period of mobility typically seen in response to emotional or physical stress. To explain this phenomenon, called paradoxical kinesia, it has been suggested that patients with PD have intact motor programs but have difficulty accessing them without an external trigger. However, external sensory (auditory or visual) stimulation may be able to activate these motor programs. This observation suggests that structures responsible for the integration of emotional, sensory and motor information must be activated to produce paradoxical kinesia. Regarding to auditory stimulation the inferior colliculus (IC) raises as an important structure that may influence paradoxical kinesia since it plays a role in sensorimotor gating activated by emotional stimuli. Therefore it is possible that the IC can be recruited during paradoxical kinesia. In the present proposal we hypothesize that electrical stimulation in an inhibitory frequency or microinjection of glutamatergic antagonists into the IC may reduce neural and motor dysfunctions as induced by temporary (haloperidol) or chronic (6-OHDA or MPTP) DA deficits in the basal nuclei. Specifically, we will test the hypothesis that appropriate modulation of an alternative and sensory-motor related pathway can access motor programs allowing akinetic animals to move, and that the IC is part of this pathway. Testing our hypothesis in animals showing motor impairments induced by temporary and chronic DA deficits will contribute to validate a new animal model of paradoxical kinesia. In parallel to behavioural analysis, we aim to assess intrastriatal neural activity, more specifically the frequency of spikes and burst activity. Here, we will determine whether the impairment-inducing manipulations (haloperidol or neurotoxin) lead to the expected changes in electrical activity in the striatum (reduced spike rate and burst activity) and whether our experimental therapeutic approaches (electrical or neurochemical inhibition within the IC) can re-establish normal activity both, neuronally and behaviorally. Importantly, all experiments will be performed using a new, bidirectional telemetric recording/stimulation system (BTSR) which allows direct comparisons between treatments, and their behavioral and neural outcomes in awake, freely-moving rodents.

• DFG Programme: Research Grants