Spatiotemporal Coupling between Hippocampal Acetylcholine Release and Theta OscillationsIn Vivo

Abstract

Both acetylcholine (ACh) and theta oscillations are important for learning and memory, but the dynamic interaction between these two processes remains unclear. Recent advances in amperometry techniques have revealed phasic ACh releases in vivo. However, it is unknown whether phasic ACh release co-occurs with theta oscillations. We investigated this issue in the CA1 region of urethaneanesthetized male rats using amperometric and electrophysiological recordings. We found that ACh release was highly correlated with the appearance of both spontaneous and induced theta oscillations. Moreover, the maximal ACh release was observed around or slightly above the pyramidal layer. Interestingly, such release lagged behind theta initiation by 25-60 s. The slow ACh release profile was matched by the slow firing rate increase of a subset of medial-septal low-firing-rate neurons. Together, these results establish, for the first time, the in vivo coupling between phasic ACh release and theta oscillations on spatiotemporal scales much finer than previously known. These findings also suggest that phasic ACh is not required for theta initiation and may instead operate synergistically with theta oscillations to promote neural plasticity in the service of learning and memory.

Vestibular stimulation enhances hippocampal long-term potentiation via activation of cholinergic septohippocampal cells

“…A theta rhythm was observed during passive rotation [33] and walking while large irregular activity was observed during immobility [28,78]. Walking [27] and caloric vestibular stimulation [34,35] were shown to increase acetylcholine level in the hippocampus, and a high acetylcholine level was associated with the presence of a theta rhythm [28,36,37,78,79]. We showed here that cholinergic activation during a rotation-induced theta rhythm is required for the enhancement of LTP.…”

“…The increase in acetylcholine level in the hippocampus following caloric vestibular stimulation [34,35] was inferred to induce an atropine-sensitive theta rhythm during passive rotation [33]. Under urethane anesthesia, the dominant hippocampal theta rhythm is atropine-sensitive and its frequency or presence correlated with acetylcholine release [36,37].…”

Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus

“…These plastic states are associated with hippocampal theta oscillations (10). High theta states are characterized by increased release of ACh that varies in a task-dependent manner on the time scale of seconds (11)(12)(13). In contrast, reduced cholinergic activity allows effective spread of excitation in the recurrent CA3 network, giving rise to synchronous sharp wave ripples (SPW-R) (14)(15)(16).…”

Decoupling of Acetylcholine Influx and Theta Power in the Hippocampus

“…Based on previous work, it would be predicted that under anesthesia (where theta is cholinergic-dependent), ACh concentration should covary with hippocampal theta power. Recent work published in The Journal of Neuroscience by Zhang et al (2010) used a novel amperometric technique to concurrently record CA1 field potentials and choline concentration in the urethaneanesthetized rat to address the temporal relationships between theta power and ACh concentration in the hippocampus, furthering our understanding of the role ACh in hippocampal theta oscillations.…”

“…This is an unexpected conclusion because hippocampal theta oscillations in urethane-anesthetized rats have previously been shown to require ACh (Kramis et al, 1975;Yoder and Pang, 2005). The proposal made by Zhang et al (2010) seems to be based on the assumption that the ACh release in CA1 needs to exhibit the same time course as the simultaneously recorded theta power for ACh to participate in theta generation. This estimate does not take into account the choline already in CA1 because the particular coating technique can only detect changes in choline concentration, not its absolute concentration.…”