Age-dependent neural coding in the basal forebrain during a Pavlovian task
Acetylcholine mediates multitude of cognitive functions including arousal, attention, sensory processing, reinforcement expectation, reward and addiction. The basal forebrain cholinergic input to the cortical mantle plays a central role in these modulatory processes. Age-related changes in the morphology of cholinergic neurons has been observed across species, characterized by dendritic, synaptic, and axonal degeneration. However, the link between cholinergic activity during learning and the normal or pathological age-related neurodegeneration is still missing. To clarify the role of the basal forebrain neurons in learning during the normal aging process, we performed neuronal recordings in the nucleus of the horizontal limb of the diagonal band, in head-fixed ChAT-cre mice during an auditory cued-outcome task. Animals from 3 to 18+ months of age were injected with an adeno-associated virus carrying channelrhodopsin-2, transfecting cholinergic neurons, allowing us to optically tag them. Animals showed decreased anticipatory licking correlated with aging, being old animals less likely to lick during reward-predicting trials, compared to young ones. Surprisingly, tagged cholinergic neurons in the young animals seemed to respond to the reward but not punishrelated cue, whereas in the old animals no response to tone was observed. Additionally, both punishment and reward activated part of the recorded neurons in all the animal groups, while only from 12+ months these contingencies had an inhibitory effect on the cell population. These changes in coding of outcome contingencies of basal forebrain neurons can reflect the ongoing degenerative process or even be the cause, at least partially, of the learning deficits observed during natural aging.