PMC

Description of stereotaxic coordinates from bregma and features of the guide cannula and injector.

mGluR5 antagonism on posterior parietal cortex does not change locomotor activity or rotarod performance. Graphs show distance traveled (A) and the percentage of distance traveled in the center of the apparatus (C) by mice injected with either vehicle (n = 6) or MPEP (n = 6) measured at 5 min intervals. Graphs show total distance traveled (B) and the percentage of distance traveled in the center (D) by mice injected with either vehicle (n = 6) or MPEP (n = 6) cumulative over 60 min. Animals were placed in the open field box after 10 min of either vehicle (DMSO 50%) or MPEP (25 nmol/0.5 μL/side) microinfusion into the parietal cortex. Each animal was monitored for 60 min. (E) Shown is a photomicrography of a representative neutral red stained coronal brain section depicting guide cannula placement according to posterior parietal cortex coordinates. (F) Graph shows latency to fall from accelerating rotarod by mice injected with either vehicle (n = 6) or MPEP (25 nmol/0.5 μL/side) (n = 6). Each animal was tested in three trials and the average latency to fall was determined. Data represent the means ± SEM.

Acute antagonism of mGluR5 on dorsolateral striatum increases locomotor activity. Graphs show distance traveled (A) and the percentage of distance traveled in the center of the apparatus (C) by mice injected with either vehicle (n = 6) or MPEP (n = 6) measured at 5 min intervals. Graphs show total distance traveled (B) and the percentage of distance traveled in the center (D) by mice injected with either vehicle (n = 6) or MPEP (n = 6) cumulative over 60 min. Animals were placed in the open field box after 10 min of either vehicle (DMSO 50%) or MPEP (25 nmol/0.5 μL/side) microinfusion into the dorsolateral striatum. Each animal was monitored for 60 min. (E) Shown is a photomicrography of a representative neutral red stained coronal brain section depicting guide cannula placement according to dorsolateral striatum coordinates. (F) Graph shows latency to fall from accelerating rotarod by mice injected with either vehicle (n = 7) or MPEP (25 nmol/0.5 μL/side) (n = 7). Each animal was tested in three trials and the average latency to fall was determined. Data represent the means ± SEM. ^* indicates significant difference as compared to vehicle-injected mice (P < 0.05).

MPEP acute antagonism on dorsal hippocampus induces increased locomotor activity. Graphs show distance traveled (A) and the percentage of distance traveled in the center of the apparatus (C) by mice injected with either vehicle (n = 6) or MPEP (n = 7) measured at 5 min intervals. Graphs show total distance traveled (B) and the percentage of distance traveled in the center (D) by mice injected with either vehicle (n = 6) or MPEP (n = 7) cumulative over 60 min. Animals were placed in the open field box after 10 min of either vehicle (DMSO 50%) or MPEP (25 nmol/0.5 μL/side) microinfusion into the hippocampus. Each animal was monitored for 60 min. (E) Shown is a photomicrography of a representative neutral red stained coronal brain section depicting guide cannula placement according to dorsal hippocampus coordinates. (F) Graph shows latency to fall from accelerating rotarod by mice injected with either vehicle (n = 6) or MPEP (25 nmol/0.5 μL/side) (n = 7). Each animal was tested in three trials and the average latency to fall was determined. Data represent the means ± SEM. ^* indicates significant difference as compared to vehicle-injected mice (P < 0.05).

The focal inhibition of mGluR5 on the olfactory bulb alters locomotor performance and distance traveled in the center of the arena. Graphs show distance traveled (A) and the percentage of distance traveled in the center of the apparatus (C) by mice injected with either vehicle (n = 7) or MPEP (n = 8) measured at 5 min intervals. Graphs show total distance traveled (B) and the percentage of distance traveled in the center (D) by mice injected with either vehicle (n = 7) or MPEP (n = 8) cumulative over 60 min. Animals were placed in the open field box after 10 min of either vehicle (DMSO 50%) or MPEP (25 nmol/0.5 μL/side) microinfusion into the olfactory bulb. Each animal was monitored for 60 min. (E) Shown is a photomicrography of a representative neutral red stained coronal brain section depicting guide cannula placement according to olfactory bulb coordinates. (F) Graph shows latency to fall from accelerating rotarod by mice injected with either vehicle (n = 7) or MPEP (25 nmol/0.5 μL/side) (n = 7). Each animal was tested in three trials and the average latency to fall was determined. Data represent the means ± SEM. ^* indicate significant differences as compared to vehicle-injected mice (P < 0.05).

The inhibition of mGluR5 on ventral striatum promotes a reduction in locomotor activity. Graphs show distance traveled (A) and the percentage of distance traveled in the center of the apparatus (C) by mice injected with either vehicle (n = 6) or MPEP (n = 6) measured at 5 min intervals. Graphs show total distance traveled (B) and the percentage of distance traveled in the center (D) by mice injected with either vehicle (n = 6) or MPEP (n = 6) cumulative over 60 min. Animals were placed in the open field box after 10 min of either vehicle (DMSO 50%) or MPEP (25 nmol/0.5 μL/side) microinfusion into the ventral striatum. Each animal was monitored for 60 min. (E) Shown is a photomicrography of a representative neutral red stained coronal brain section depicting guide cannula placement according to ventral striatum coordinates. (F) Graph shows latency to fall from accelerating rotarod by mice injected with either vehicle (n = 8) or MPEP (25 nmol/0.5 μL/side) (n = 7). Each animal was tested in three trials and the average latency to fall was determined. Data represent the means ± SEM. ^* indicates significant difference as compared to vehicle-injected mice (P < 0.05).

mGluR5 blockage in the primary motor cortex promotes reduction of both locomotor activity and rotarod performance. Graphs show distance traveled (A) and the percentage of distance traveled in the center of the apparatus (C) by mice injected with either vehicle (n = 7) or MPEP (n = 8) measured at 5 min intervals. Graphs show total distance traveled (B) and the percentage of distance traveled in the center (D) by mice injected with either vehicle (n = 7) or MPEP (n = 8) cumulative over 60 min. Animals were placed in the open field box after 10 min of either vehicle (DMSO 50%) or MPEP (25 nmol/0.5 μL/side) microinfusion into the primary motor cortex. Each animal was monitored for 60 min. (E) Shown is a photomicrography of a representative neutral red stained coronal brain section depicting guide cannula placement according to primary motor cortex coordinates. (F) Graph shows latency to fall from accelerating rotarod by mice injected with either vehicle (n = 7) or MPEP (25 nmol/0.5 μL/side) (n = 7). Each animal was tested in three trials and the average latency to fall was determined. Data represent the means ± SEM. ^* indicate significant differences as compared to vehicle-injected mice (P < 0.05).

Potential neural pathways involved in motor behavior modulated by mGluR5. (A) Shows schematic representing CNS regions where MPEP injections were performed and the possible neural pathways involved in the behavioral findings following mGluR5 blockage. (1) MPEP injection on the main olfactory bulb (MOB) led to an increase in the distance traveled in the center of the arena and to decreased motor performance on the rotarod. (2) MPEP injection into the primary motor area (M1) led to a decrease in locomotion in the open field and to decreased rotarod performance. (3) The blockage of mGluR5 in the dorsolateral striatum (DLStr) led to increased locomotor activity. Inhibition of mGluR5 by MPEP in DLStr (Green lines) may disinhibit the globus pallidus externa (GPe), which can then inhibit the subthalamic nucleus (STN). STN inhibition will diminish activation of the substantia nigra pars reticulata (SNr)/ globus pallidus interna (GPi), with consequent disinhibition of the thalamus (Th) – cerebral cortical (Cx) circuit, resulting in increased locomotor activity. (4) The blockage of mGluR5 in the ventral striatum (VStr) by MPEP (pink lines) may disinhibit the SNr, which can inhibit Th-Cx projections, resulting in decreased locomotor activity. (5) mGluR5 inhibition in the dorsal hippocampus (dHPC) resulted in increased locomotor activity. The dHC projects to the VStr, which is involved in motor control (orange lines). Moreover, it has been shown that the dHPC has intrahippocampal projections connecting it to the ventral hippocampus (vHPC). (6) MPEP injections on the posterior parietal cortex (V2MM) elicited no alteration on behavioral tests. (B) Shows summary results of the behavioral findings for each neural substrate injected with MPEP. Blue circles indicate brain regions that highly express mGluR5 and that were injected with MPEP. Colorful lines (green, pink and orange) represent neural circuits. Filled lines indicate activated circuits and dotted lines indicate inhibited circuits. Excitatory pathways are depicted as arrows and inhibitory pathways as blocked lines.