Cannabis is one of the most commonly used illicit substances worldwide. Cannabis is also popular in the US among pregnant women to reduce morning sickness related symptoms. Prenatal cannabinoid exposure (PCE) can cause long term neurofunctional and cognitive alterations. This study investigates the mechanisms of learning and memory deficits associated with PCE in the offspring. Pregnant dams were administered synthetic cannabinoid agonist WIN55,212-2 and a series of behavioral, electrophysiological, and immunochemical studies were performed to identify and determine the potential cause of memory deficits in the adolescent offspring. Findings revealed that, the behavioral deficits observed in the PCE offspring were due to decreased long-term potentiation (LTP) and enhanced long-term depression (LTD) at hippocampal Schaffer collateral-CA1 synapses, along with an altered glutamatergic downstream signaling. PCE reduced gene and protein expression of neural cell adhesion molecule (NCAM) and polysialylated-NCAM (PSA-NCAM), which are critical for GluN2A and GluN2B signaling balance. Administration of exogenous PSA restored the LTP deficits observed in PCE animals. In summary, PSA mediated alterations in glutamatergic signaling pathways may be responsible for the impaired hippocampal synaptic plasticity and memory deficits resulting from PCE. These findings enhance our current understanding of PCE mediated memory deficits and will assist to target for future therapeutic purposes.