Haloperidol–induced catalepsy is ameliorated by deep brain stimulation of the inferior colliculus

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.

In vivo Probabilistic Structural Atlas of the Inferior and Superior Colliculi, Medial and Lateral Geniculate Nuclei and Superior Olivary Complex in Humans Based on 7 Tesla MRI

“…Upon its release on public repositories of neuroimaging data and tools, this atlas might be used as a tool to better identify the IC, SC, MG, LG, SOC nuclei location in conventional (e.g., 3 Tesla) MRI, and enable more accurate characterizations of auditory and visual connectivity pathways in fMRI and diffusion tractography studies. The current work provides a detailed description of the location, shape and anatomy of these nuclei that could be useful in research as well as in future clinical studies to aid treatment delivery and tuning of strategies such as repetitive transcranial magnetic stimulation, neurosurgical planning or focused ultrasound therapies i.e., in tinnitus treatment (Smit et al, 2016; Yilmaz and Yilmaz, 2018) or advanced stages of Parkinson’s disease with catalepsy symptoms (Engelhardt et al, 2018). This atlas could also be used to evaluate microstructural changes in the brainstem, such as the location of microbleeds/lesions/tumors.…”

Low frequency deep brain stimulation in the inferior colliculus ameliorates haloperidol-induced catalepsy and reduces anxiety in rats

“…We have shown that high-frequency DBS in the inferior colliculus (IC), a midbrain structure classically related to auditory processing, can serve as an alternative DBS target to ameliorate motor deficits in akinetic rats [ 9 , 10 ]. The IC is an important relay station for ascending and descending auditory information but is distinguished from other brainstem auditory nuclei by its indirect projections to motor pathways [ 11 ].…”

Deep cerebellar stimulation reduces ataxic motor symptoms in the shaker rat

“…21 Tenkilohertz stimulation is effective for spinal cord stimulation for chronic leg and back pain, 22 and sub-50 Hz stimulation can be effective for stroke recovery, 15,16 chronic pain, 23 and catalepsy. 24 Certain parameters improve some symptoms while worsening others; high-frequency stimulation for primary parkinsonism symptoms exacerbates vocalization deficits. 25,26 We hypothesized that low-frequency stimulation would be most effective for ataxia because low-frequency stimulation enhances network throughput, 16,27 whereas high-frequency stimulation functions as an informational lesion.…”

“…Parkinsonian DBS is usually >100 Hz, although 60 Hz can effectively treat bradykinesia . Ten‐kilohertz stimulation is effective for spinal cord stimulation for chronic leg and back pain, and sub‐50 Hz stimulation can be effective for stroke recovery, chronic pain, and catalepsy . Certain parameters improve some symptoms while worsening others; high‐frequency stimulation for primary parkinsonism symptoms exacerbates vocalization deficits .…”