Dynamics of septo-hippocampal cholinergic activity in response to environmental context change and during goal-oriented learning
Elevated cholinergic tone has been associated with cortical activation during arousal, attention, and learning. Acetylcholine (ACh) is thought to enhance neuronal responses to sensory stimuli and facilitate plasticity during encoding of novel information. One of the main targets of cholinergic modulation is the hippocampus (HC), a cortical region critical for spatial and episodic memory formation in the mammalian brain. Perturbations of cholinergic modulation to the HC cause severe deficits in spatial navigation and hippocampal learning. However, the dynamics of hippocampal cholinergic input from the medial septum, the main source of ACh in the HC, during different behaviors are still unclear. Using in vivo 2-photon imaging in dorsal HC CA1 of head-restrained awake mice, we recorded calcium activity of cholinergic axonal projections with single-fiber resolution. Cholinergic neurons of the medial septum were selectively labeled with the functional calcium indicator GCaMP6f via viral gene transfer and using transgenic ChAT-Cre mice. Calcium dynamics of septo-hippocampal cholinergic fibers were recorded during exploration of different multisensory contexts and in a goal-oriented spatial learning paradigm (Danielson et al, 2016). We found that septo-hippocampal cholinergic fibers were activated by locomotion and upon exposure to novel multimodal contexts. Moreover, in spatial learning, calcium activity of cholinergic axons was elevated in the initial learning phase of the task but decreased as the reward location was learnt. With detailed analysis, we aimed to decipher the fine-grained pattern of cholinergic activity in correlation with the various stages of hippocampal information processing and behavior.