Phasic modulation of hippocampal synaptic plasticity by theta rhythm.

Theta rhythm and long-term potentiation (LTP) are 2 remarkable discoveries. The theta rhythm is an oscillatory neural activity of 3-10 Hz in the hippocampus. LTP is implicated as a cellular basis of memory, but the function of theta oscillation in memory is not clear. This review suggests that theta rhythm bestows optimal conditions for hippocampal LTP and memory encoding. Theta rhythm in hippocampal CA1 is generated mainly by 2 oscillating dipoles-somatic-inhibition and phase-shifted, distal dendritic excitation, with a smaller contribution by rhythmic proximal (CA3) excitation and distal inhibition. Our recent study showed that LTP of the excitatory synapses on the basal or apical dendrites of CA1 pyramidal cells peaked twice in a theta cycle, at the rising (R) and the midcycle (M) phase of the theta rhythm recorded at the distal apical dendrites. In contrast, evoked population spike excitability peaked at a single phase near the midcycle. We infer that R and M peaks of LTP correspond to maximal dendritic depolarization and maximal somatic depolarization of CA1 pyramidal cells, respectively. A ∼50° phase shift between LTP-versus-theta-phase functions suggests independent LTP at the basal and apical dendrites. It is argued that theta phase-dependent LTP occurs under physiological conditions, by pairing presynaptic activity with oscillating postsynaptic depolarization. Place cells, showing intrinsic membrane potential oscillations, are ideal LTP participants. It is suggested that theta phase-dependent LTP contributes to memory encoding, and disruption of either theta oscillation or LTP may disrupt memory in various neurological disorders, including epilepsy and Alzheimer's disease. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Long-Term Potentiation and Excitability in the Hippocampus Are Modulated Differently by θ Rhythm.

Oscillations in the brain facilitate neural processing and cognitive functions. This study investigated the dependence of long-term potentiation (LTP), a neural correlate of memory, on the phase of the hippocampal θ rhythm, a prominent brain oscillation. Multichannel field potentials and current source-sinks were analyzed in hippocampal CA1 of adult male rats under urethane anesthesia. A single burst (five pulses at 200 Hz) stimulation of stratum oriens (OR) induced LTP of the basal dendritic excitatory sink (ES), which was maximal when the burst was delivered at ∼340° and ∼160° of the distal dendritic θ rhythm. Apical dendritic sink evoked by stratum radiatum (RAD) stimulation also showed biphasic maxima at ∼30° and ∼210° of the distal dendritic θ rhythm, about 50° phase delay to basal dendritic LTP. By contrast, maximal population spike (PS) excitability, following single-pulse excitation of the basal or mid-apical dendrites, occurred at a θ phase of ∼140°, and maximal basal dendritic ES occurred at ∼20°; γ (30-57 Hz) activity recorded in CA1 RAD had maximal power at ∼300° of the distal dendritic θ rhythm, different from the phases of maximal LTP. LTP induced during the rising θ phase was NMDA receptor sensitive. It is suggested that the θ phase modulation of CA1 PS excitability is mainly provided by θ-rhythmic proximal inhibition, while dendritic LTP is also modulated by dendritic inhibition and excitation, specific to basal and apical dendrites. In summary, basal and apical dendritic synaptic plasticity and spike excitability are facilitated at different θ phases in a compartmental fashion.

Regulation of Cognitive Processing by Hippocampal Cholinergic Tone.

Cholinergic dysfunction has been associated with cognitive abnormalities in a variety of neurodegenerative and neuropsychiatric diseases. Here we tested how information processing is regulated by cholinergic tone in genetically modified mice targeting the vesicular acetylcholine transporter (VAChT), a protein required for acetylcholine release. We measured long-term potentiation of Schaffer collateral-CA1 synapses in vivo and assessed information processing by using a mouse touchscreen version of paired associates learning task (PAL). Acquisition of information in the mouse PAL task correlated to levels of hippocampal VAChT, suggesting a critical role for cholinergic tone. Accordingly, synaptic plasticity in the hippocampus in vivo was disturbed, but not completely abolished, by decreased hippocampal cholinergic signaling. Disrupted forebrain cholinergic signaling also affected working memory, a result reproduced by selectively decreasing VAChT in the hippocampus. In contrast, spatial memory was relatively preserved, whereas reversal spatial memory was sensitive to decreased hippocampal cholinergic signaling. This work provides a refined roadmap of how synaptically secreted acetylcholine influences distinct behaviors and suggests that distinct forms of cognitive processing may be regulated in different ways by cholinergic activity.