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The basal forebrain is the one of the main sites of acetylcholine (ACh) production, projecting to various regions throughout the brain. The cholinergic system has been shown to contribute to important cognitive processes, such as attention and memory. Previous findings suggest that basal forebrain projections form non-synaptic connections and only release one neurotransmitter. However, a recently published paper in Nature Communications from Gabor Nyiri’s lab at the Hungarian Academy of Sciences challenged these assumptions by demonstrating that these basal forebrain projections to the hippocampus show different characteristics.

Takacs et al. first demonstrated that cholingeric fibers projecting from the basal forebrain form synaptic connections in the hippocampus. In addition, these synaptic connections are not limited to only acetylcholine release, but also release GABA, suggesting that these basal forebrain projections co-transmit these two neurotransmitters. To investigate the electrophysiological characteristics of hippocampal cells, the authors expressed ChR2 in these basal forebrain neurons. Widefield optogenetic stimulation of these basal forebrain projections in the hippocampus elicited a response in neurons that was suggestive of both ACh and GABA release.

Subsequently, GABAergic responses (in the presence of blocked nicotinic and muscarinic receptors) produced by optogenetic stimulation of these cholingeric basal forebrain projections showed short-term depression (SDT). The authors proposed that this STD response may be due to influx of calcium through ChR2 channels expressed in the cholingeric terminals. To eliminate this possibility, Takacs et al. used Mightex’s DMD-based Polygon400 pattern illuminator to target the optogenetic illumination to specific regions, rather than the entire area (see Figure 1). Only the projecting fibers, not the terminals, entering the hippocampus from the basal forebrain were illuminated. Takacs et al. showed the same effects as above, demonstrating that this STD response was not due to influx of calcium.

Takacs et al. demonstrated a novel mechanism through which cholingeric projections form synaptic connections and co-transmit GABA, as well as ACh. Their findings also demonstrate how this novel mechanism can alter network activity in the hippocampus, and they suggest this could lead to new potential phamacotherapies for Alzheimer’s Disease. Lastly, the author’s show a novel use for the Polygon400 patterned illuminator as a control for illuminating specific regions of cells, rather than the entire area of interest.

To learn more about the Polygon400, click here. Or, read our white paper comparing tools for single-cell resolution optogenetics.

To read the full paper published in Nature Communications, click here.

Takacs, V.T., Cserep, C., Schlingloff, D., Posfai, B., Szonyi, A., Sos, K.E., Kornyei, Z., Denes, A., Gulyas, A., Freund, T.F., & Nyiri, G. (2018). Co-transmission of acetylcholine and GABA regulates hippocampal states. Nature Communications.

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