Cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD (Han, 2012):
The hippocampus is an area of the brain that contains a high concentration of cannabinoid receptors and is involved in the formation of memories. Long-term depression (LTD) is a form of synaptic plasticity (cell signaling between neurons) that involves persistent weak synaptic stimulation that ultimately leads to decreased efficacy at a synaptic connection by decreasing a cell’s likelihood of firing. Conversely, Long-term Potentiation (LTP) is a form of synaptic plasticity that increases the likelihood of a cell to fire.
Both LTP and LTD are processes that contribute to memory formation and LTD specifically is altered by the activation of Cannabinoid Type 1 Receptors (CB1Rs) in the hippocampus. In this study researchers studied the connections between CA1 and CA3 regions of the hippocampus to determine what cell type was causing this difference.
To study these connections, researchers selectively blockaded CB1R’s in specific subtypes of neurons. In this case they blocked CB1R’s on glutaminergic neurons, GABAergic neurons, and non-neuronal cells called astrocytes. By selectively blocking each type in mice and subsequently observing their performance in a memory test researchers were able to determine the subtype of brain cell that caused this deficit in memory.
In summary: “We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB1R and is associated with astroglia-dependent hippocampal LTD in vivo.”