Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04

    • In these experiments recordings were performed continuously

    2023-07-28

    In these experiments, recordings were performed continuously in the homecage and during the first 5 days of training on a randomized forced alternation T-maze working memory task (Figures 1A, 1B, 3A, and 3B) (Kucewicz et al., 2011). Sleep and wake states were determined by simultaneous recording of hippocampal LFP and locomotor activity combined with the automated sleep scoring algorithm based on SCORE (Van Gelder et al., 1991) (Figures 1B and 1C). By this method, states were designated as active or quiet wakefulness and REM or NREM sleep. Epochs classified as sleep often contained multiple REM and NREM episodes interleaved with quiet wakefulness (Figure 1D). Tonic and phasic release are here referred to, respectively, as desynchronized firing of cholinergic terminals on the scale of tens of seconds to minutes, leading to a slow changing, sustained extracellular cholinergic signal; and as synchronous firing across the population of cholinergic inputs, generating fast extracellular Retigabine dihydrochloride transients detected on the scale of milliseconds to seconds. These release profiles were clearly distinguished with halfwidths >30 s (tonic) and <5 s (phasic) (Sarter et al., 2009).
    Discussion In this study, we made continuous recordings of acetylcholine release dynamics across a wide temporal range and simultaneously in two brain regions, the mPFC and dHPC. We confirmed that acetylcholine release can be classified into phasic and tonic modes that occur on distinct timescales and perform different roles (Sarter et al., 2009). We found that the two modes of transmission are not unique to the neocortex and also occur in the hippocampus. Tonic release was associated with arousal and the transition between specific vigilance states, whereas phasic release only occurred during behavior with the highest levels of arousal, i.e., while performing a cognitive task, where it occurred preferentially at the reward delivery locations. Surprisingly, both modes of transmission were coordinated between the mPFC and dHPC, indicating a brain-wide cholinergic signal. Transitions into REM sleep or high-arousal states such as wakefulness are characterized by a switch from low-frequency oscillations to high-frequency oscillations or desynchronized neuronal networks that are also a feature of selective attention (Hasselmo and Sarter, 2011) and the selection of salient information relevant to reinforcement cues such as reward or punishment (Hangya et al., 2015; Lovett-Barron et al., 2014). This is thought to occur by increasing the signal-to-noise ratio of sensory input in primary sensory cortices (Chen et al., 2015; Eggermann et al., 2014; Fu et al., 2014; Pinto et al., 2013). It is proposed that a common mechanism underlying these states is increased acetylcholine release (Harris and Thiele, 2011). Using continuous recordings across multiple brain states, we aimed to determine whether acetylcholine release correlates with these behavioral states. We show that acetylcholine release is strongly associated with high-arousal states and location of the animal in the reward delivery area on a T-maze spatial working memory task, suggesting that acetylcholine is released in response to reward or the expectation of reward. These observations broadly support a role for cholinergic input for the desynchronization of networks during increases in arousal or attentional states. Specifically, we show a conditional and coordinated increase in tonic acetylcholine during REM sleep, which suggests that acetylcholine may be preparing mPFC and dHPC networks simultaneously for wakefulness (Jones, 2004) and the enhanced vigilance required for the performance of tasks requiring sustained attention (Paolone et al., 2012). Although it is likely that GABAergic projections control switching between behavioral states (Anaclet et al., 2015; Chen et al., 2016), cholinergic inputs play the role in network state modulation (Fisahn et al., 1998; Lee et al., 1994). In addition, our continuous recordings of acetylcholine release with high temporal resolution show that REM sleep cannot be classified as a single homogeneous state and that REM epochs occurring in the middle of NREM epochs may be performing roles different from those occurring immediately before wakefulness. The underlying mechanism for REM epoch heterogeneity may result from the complexity of brainstem circuitry controlling REM sleep initiation and maintenance (Saper et al., 2010). The core finding that the magnitude of tonic acetylcholine release during REM is predictive of subsequent wakefulness demonstrates a previously unappreciated role for acetylcholine release during REM sleep.