Background
Cannabis, marijuana or cannabinoids (compounds found in cannabis), produce analgesia effects and modulate vomiting, seizures, ischemia, cerebral trauma, mood and tumors in both humans and animals. However, heavy marijuana use can result in transient motor suppression, transient memory impairment and dependence in a significant subset of humans. How cannabis produces these effects is not clear. Cannabinoids act on type 1 and type 2 cannabinoid receptors, i.e., CB1R and CB2R, which are mainly distributed in the brain and peripheral immune system, respectively. Since the discovery of CB1R and CB2R in 1990s, our brain has been found to contain endogenous cannabinoids or endocannabinoids (chemicals with action similar to cannabinoids).
Our brain consists of two main cell types, neurons and glial cells. Neurons communicate to each other via synapses that transmit information from the axon of one neuron to the dendrite of another neuron. Both excitatory glutamatergic and inhibitory GABAergic transmission at synapses can be transient or long-term, which are modulated by CB1R located in excitatory and inhibitory presynaptic terminals as well as in glial cells. Activity- or experience-dependent enhancement and weakening of synaptic strength, i.e. long-term potentiation (LTP) and long-term depression (LTP), respectively, plays important roles in drug addiction, memory processing and mood modulation through mechanisms that are far from being fully understood.
Specific aims
Our research is to explore how cannabinoids and endocannabinoids modulate reward, memory and mood through LTD/LTP induction as a result of their actions on CB1Rs in both presynaptic terminals and astrocyte-type of glial cells. Specifically, we are determining the contributions of cannabinoid- and endocannabinoid-induced LTD/LTP at midbrain and hippocampal synapses to cannabinoid addiction, working memory performance, fear memory extinction and anxiety/depression development. These studies are performed simultaneously on four platforms employing molecular/biochemical, electrophysiological, neuroanatomical and behavioral strategies.