Abstract
Deep brain stimulation (DBS) has evolved as a promising alternative treatment for Parkinson’s disease (PD), but the underlying mechanisms remain poorly understood. Moreover, conventional DBS protocols targeted at basal ganglia sites can turn out completely ineffective for some PD patients, warranting the search for alternative targets. The inferior colliculus (IC) is a midbrain auditory relay station involved in sensorimotor processes. High-frequency 2500 Hz electrical stimulation of the IC elicits escape behaviour and interferes with haloperidol-induced catalepsy in rats, a state reminiscent of Parkinsonian akinesia, but clinical implication is limited since the protocol is aversive. However, typical DBS stimulation frequencies range between 20–180 Hz. We therefore tested the effects of a low-frequency 30 Hz-DBS protocol on haloperidol-induced catalepsy and aversive behaviour in rats. We show that low-frequency 30 Hz-DBS targeted at the IC strongly ameliorates haloperidol-induced catalepsy without any evidence of stimulation-induced escape behaviour. Furthermore, 30 Hz-DBS of the IC produced no place avoidance in a place conditioning paradigm and induced no anxiety-related behaviour on the elevated plus maze, indicating that the protocol has no aversive or anxiogenic side effects. Our findings provide first evidence that the IC can serve as an alternative, non-conventional DBS target.
Highlights
Deep brain stimulation (DBS) has evolved as a promising treatment strategy for severe cases of Parkinson’s disease (PD), a neurodegenerative movement disorder characterized by tremor, rigidity, and bradykinesia/akinesia[1]
Since typical DBS stimulation frequencies range between 20–180 Hz3,17,18, we asked whether low-frequency 30 Hz-DBS of the inferior colliculus (IC) can reduce haloperidol-induced catalepsy without aversive side effects
Low-frequency deep brain stimulation of the IC ameliorates akinesia-like motor deficits
Summary
Deep brain stimulation (DBS) has evolved as a promising treatment strategy for severe cases of Parkinson’s disease (PD), a neurodegenerative movement disorder characterized by tremor, rigidity, and bradykinesia/akinesia[1]. High-frequency 2500 Hz electrical stimulation of the IC at specific current thresholds elicits escape behaviour[12,13] and we recently showed that such stimulation at these thresholds induces vigorous escape responses in rats treated with haloperidol, thereby releasing the cataleptic state[15]. Such an effect is reminiscent of a clinical phenomenon known as paradoxical kinesia, i.e. the sudden and transient ability of akinetic PD patients to perform coordinated movements (e.g. flight reactions) in response to an emotionally significant trigger, such as emotional stress[16]. This is the case for structures located outside the basal ganglia, such as the pedunculopontine nucleus, another brainstem structure involved in motor behaviour besides the IC, where optimal stimulation frequencies range between 20–80 Hz18,19
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