Altering Opioid Neuromodulation in the Songbird Basal Ganglia Modulates Vocalizations.

Niranjan Ashok Kambi,Sandeep Kumar,Soumya Iyengar,Raghav Rajan,Thirumurthy Velpandian,Utkarsha A. Singh,Alok Nath Mohapatra,Hanuman Prasad Sharma

doi:10.3389/fnins.2019.00671

Abstract

Although the interplay between endogenous opioids and dopamine (DA) in the basal ganglia (BG) is known to underlie diverse motor functions, few studies exist on their role in modulating speech and vocalization. Vocal impairment is a common symptom of Parkinson’s disease (PD), wherein DA depletion affects striosomes rich in μ-opioid receptors (μ-ORs). Symptoms of opioid addiction also include deficiencies in verbal functions and speech. To understand the interplay between the opioid system and BG in vocalization, we used adult male songbirds wherein high levels of μ-ORs are expressed in Area X, a BG region which is part of a circuit similar to the mammalian thalamocortical-basal ganglia loop. Changes in DA, glutamate and GABA levels were analyzed during the infusion of different doses of the μ-OR antagonist naloxone (50 and 100 ng/ml) specifically in Area X. Blocking μ-ORs in Area X with 100 ng/ml naloxone led to increased levels of DA in this region without altering the number of songs directed toward females (FD). Interestingly, this manipulation also led to changes in the spectro-temporal properties of FD songs, suggesting that altered opioid modulation in the thalamocortical-basal ganglia circuit can affect vocalization. Our study suggests that songbirds are excellent model systems to explore how the interplay between μ-ORs and DA modulation in the BG affects speech/vocalization.

Highlights

Previous studies demonstrated significant deficits in verbal intelligence (Prosser et al, 2006) and speech deficits in opioid addicts (Wasserman and Yahr, 1980) and as side-effects of prescription opioids
Our results suggest that μ-ORs modulate vocalization and may be partly responsible for the vocal impairments observed in drug-addicts and PD patients (Prosser et al., 2006; Rusz et al., 2015)
Taken together with these findings, our results suggest that the μ-OR and dopaminergic systems interact with each other to modulate the output of the basal ganglia

Summary

Introduction

Previous studies demonstrated significant deficits in verbal intelligence (Prosser et al, 2006) and speech deficits (slurring and/or stuttering) in opioid addicts (Wasserman and Yahr, 1980) and as side-effects of prescription opioids. Whereas most studies have explored the role of opioid modulation in reward-based learning or in motivated behaviors, its role in vocalization has not been explored thoroughly Songbirds such as zebra finches (Taenopygia guttata) which use their songs for courtship have been extensively used to study how vocalizations are learned during development and sung in different social contexts in adulthood. Both of these functions are controlled by the anterior forebrain pathway (AFP), a part of the song control system [SCS, (Nottebohm et al, 1976), Figure 1A]. Blocking μ-ORs (μ-opioid receptors) with different doses of the opioid antagonist naloxone in adult male zebra finches led to decreases in the number of songs and alterations in their acoustic features (Khurshid et al, 2010)

Methods

Results

Conclusion