Hala Haddad

Summer Research Description: Disruptions in synaptic transmission in the striatum are believed to cause a variety of neurological and psychiatric disorders, like Parkinson’s disease and autism spectrum disorders. Endocannabinoids are lipid metabolites that physiologically modulate synaptic communication through retrograde signaling in cortico-striatal pathways. Disruptions in the endocannabinoid system have been linked to striatal-based disorders. One of the endocannabinoid ligands, 2-arachidonoylglycerol (2-AG), is synthesized by diacylglycerol lipase α (DGLα), which is activated by metabotropic glutamate receptors and/or calcium influx. Specifically in the striatum, endocannabinoids are important for mediating long-term depression, a form of synaptic plasticity, in striatal neurons that comprise the direct and indirect pathways. However, the pathway-specific role of 2-AG signaling on striatal behavior is not well understood. Therefore, we utilized a mouse line where DGLα is conditionally deleted from direct or indirect pathway neurons under the direction of the Dopamine-1 and adenosine 2a receptor promoters respectively.  We are testing a range of striatal-based behaviors including motor performance, as well as habitual and repetitive behaviors in both normal conditions and dopamine depleted states (using 6-hydroxydopamine lesions). With this approach, we hope to better understand the effects of endocannabinoids on the striatum in Parkinson’s disease and autism spectrum disorders.