Priyanka Das Pinky, MBBS

Cannabis is currently the most common illicitly used drug during pregnancy. Although public opinion is that marijuana is safe to use, cannabinoids can easily cross the placenta and reach the fetal brain, affecting its neural growth and development. These effects are long-lasting and can influence various aspects of adult behavior, including learning and memory, anxiety, attention span, etc. However, there are currently no therapeutic options to treat the cognitive deficits associated with prenatal cannabinoid exposure. The goal of this study was to elucidate the mechanism by which prenatal cannabinoid exposure causes learning and memory deficits in rodent offspring and to identify therapeutic targets that can correct memory deficits. In this study, rats were treated throughout pregnancy with a synthetic cannabinoid. The offspring were then examined during their adolescence by performing various behavioral experiments, i.e., Morris water maze, Y maze, and Contextual fear conditioning, and were found to have memory deficits. Electrophysiological recording on the brain slice revealed alterations in synaptic plasticity within the hippocampus, a key area for learning and memory, that likely contributed to the observed memory deficits. Synaptic plasticity, which gives an idea about memory formation, can be defined as the ability of connections between neurons to strengthen or weaken in response to neuronal activity. Long-term potentiation (LTP) and long-term depression (LTD) are two important parameters to measure synaptic plasticity and both were impaired in these offspring. An alteration in the hippocampal glutamatergic neurotransmission has also been observed. Glutamate is the major excitatory neurotransmitter in the brain and is important for facilitating learning and formation and maintenance of memory. A major modulator of glutamatergic neurotransmission is the neural cell adhesion molecule (NCAM) that helps in neurite outgrowth, neural pathfinding, and neurogenesis. NCAM and its active form Polysialylated NCAM both were reduced in the hippocampus of prenatally cannabinoid exposed offspring. Most importantly, preliminary studies indicated that modulation of PSA-NCAM could restore the observed synaptic plasticity deficits in prenatally cannabinoid exposed offspring. The data from this study not only points toward a specific mechanism responsible for prenatal cannabinoid mediated deficits but will also comprehensively assess the different roles played by synaptic molecules responsible for plasticity mechanisms closely associated with cognition. Moreover, this will serve as an excellent premise for future interventions to restore memory functioning in individuals exposed to cannabinoids.