Chandrika Abburi, United States of America

University of Chicago Anesthesia and Critical Care
Chandrika Abburi is a research assistant professor in the department of Anesthesia and Critical Care at the University of Chicago. She has been exploring pathology-induced alterations in neural circuits in Parkinson’s disease using novel optogenetic approaches. She has gained deep understanding regarding the mechanisms involved in aberrant synaptic plasticity at corticostriatal synapses and aberrant motor learning in Parkinson’s disease (PD). She has been using optogenetic approaches to manipulate corticostriatal synapses, which reverses the aberrant synaptic plasticity and relieves motor symptoms in Parkinson’s disease.

Author Of 2 Presentations

PERSISTENT RELIEF OF MOTOR SYMPTOMS IN A PARKINSONIAN MOUSE MODEL AFTER OPTOGENETIC STIMULATION OF MOTOR CORTEX AND D2 RECEPTOR ACTIVATION

Session Type
SYMPOSIUM
Date
11.03.2021, Thursday
Session Time
12:00 - 14:00
Room
On Demand Symposia E
Lecture Time
13:15 - 13:30
Session Icon
On-Demand

Abstract

Aims

Motor deficits in Parkinson’s disease (PD) results from dopamine loss. Our earlier studies suggest an important role of task-specific aberrant inhibitory learning mediated by long-term potentiation in corticostriatal synapses onto D2 receptor expressing striatal neurons (D2-MSNs) in the absence of dopamine. We hypothesize that corticostriatal stimulation along with D2 receptor activation would reverse such aberrant plasticity and reduce motor deficits in PD.

Methods

Motor deficits of unilateral 6-OHDA lesioned mice were assessed using rotarod and rotation tests. Postmortem tyrosine hydroxylase (TH) immunostaining confirmed dopamine loss. AAV2 containing channelrhodopsin-2 was expressed in layer 5 motor cortex projection neurons. Optogenetic high-frequency stimulation (oHFS) of corticostriatal projections was combined with D2 agonist quinpirole to induce long term depression (LTD) of D2-MSN inputs. Motor performance was monitored using rotarod. Electrophysiological studies were conducted ex-vivo to assess corticostriatal plasticity and excitability of D2-MSNs in sham and lesioned animals.

Results

6-OHDA animals displaying strong motor deficits received oHFS in the dorsolateral striatum (DLS) along with quinpirole administration for 5 days. This treatment improved motor performance for over 4 weeks. oHFS or quinpirole alone did not improve the motor performance. In ex-vivo electrophysiology, oHFS-induced LTD was obtained using bath application of quinpirole in 6-OHDA mice. Consistent with LTD induction, VGLUT1 expression in DLS was reduced in combined treatment received animals.

Conclusions

Our results indicate that combination of cortical stimulation and D2 receptor activation reverses the aberrant plasticity in DLS, resulting in long-lasting improvement in motor function, suggesting an effective therapeutic approach for PD.

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Presenter of 2 Presentations

PERSISTENT RELIEF OF MOTOR SYMPTOMS IN A PARKINSONIAN MOUSE MODEL AFTER OPTOGENETIC STIMULATION OF MOTOR CORTEX AND D2 RECEPTOR ACTIVATION

Session Type
SYMPOSIUM
Date
11.03.2021, Thursday
Session Time
12:00 - 14:00
Room
On Demand Symposia E
Lecture Time
13:15 - 13:30
Session Icon
On-Demand

Abstract

Aims

Motor deficits in Parkinson’s disease (PD) results from dopamine loss. Our earlier studies suggest an important role of task-specific aberrant inhibitory learning mediated by long-term potentiation in corticostriatal synapses onto D2 receptor expressing striatal neurons (D2-MSNs) in the absence of dopamine. We hypothesize that corticostriatal stimulation along with D2 receptor activation would reverse such aberrant plasticity and reduce motor deficits in PD.

Methods

Motor deficits of unilateral 6-OHDA lesioned mice were assessed using rotarod and rotation tests. Postmortem tyrosine hydroxylase (TH) immunostaining confirmed dopamine loss. AAV2 containing channelrhodopsin-2 was expressed in layer 5 motor cortex projection neurons. Optogenetic high-frequency stimulation (oHFS) of corticostriatal projections was combined with D2 agonist quinpirole to induce long term depression (LTD) of D2-MSN inputs. Motor performance was monitored using rotarod. Electrophysiological studies were conducted ex-vivo to assess corticostriatal plasticity and excitability of D2-MSNs in sham and lesioned animals.

Results

6-OHDA animals displaying strong motor deficits received oHFS in the dorsolateral striatum (DLS) along with quinpirole administration for 5 days. This treatment improved motor performance for over 4 weeks. oHFS or quinpirole alone did not improve the motor performance. In ex-vivo electrophysiology, oHFS-induced LTD was obtained using bath application of quinpirole in 6-OHDA mice. Consistent with LTD induction, VGLUT1 expression in DLS was reduced in combined treatment received animals.

Conclusions

Our results indicate that combination of cortical stimulation and D2 receptor activation reverses the aberrant plasticity in DLS, resulting in long-lasting improvement in motor function, suggesting an effective therapeutic approach for PD.

Hide