Chandrika Abburi, United States of America
University of Chicago Anesthesia and Critical CareAuthor Of 2 Presentations
LIVE DISCUSSION
- Thorsten Mueller, Germany
- Karine Cambon, France
- Monica Van den Berg, Belgium
- Tiansheng Liu, United Kingdom
- Chandrika Abburi, United States of America
- Jeffrey N. Savas, United States of America
- Rick Livesey, United Kingdom
- David Morgan, United States of America
- David Blum, France
- Sebastiaan De Schepper, United Kingdom
PERSISTENT RELIEF OF MOTOR SYMPTOMS IN A PARKINSONIAN MOUSE MODEL AFTER OPTOGENETIC STIMULATION OF MOTOR CORTEX AND D2 RECEPTOR ACTIVATION
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.
Presenter of 2 Presentations
PERSISTENT RELIEF OF MOTOR SYMPTOMS IN A PARKINSONIAN MOUSE MODEL AFTER OPTOGENETIC STIMULATION OF MOTOR CORTEX AND D2 RECEPTOR ACTIVATION
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.
LIVE DISCUSSION
- Thorsten Mueller, Germany
- Karine Cambon, France
- Monica Van den Berg, Belgium
- Tiansheng Liu, United Kingdom
- Chandrika Abburi, United States of America
- Jeffrey N. Savas, United States of America
- Rick Livesey, United Kingdom
- David Morgan, United States of America
- David Blum, France
- Sebastiaan De Schepper, United Kingdom