Abstract:Calcium is a critical second messenger in neurons that contributes to learning and memory, but how the coordination of action potentials of neuronal ensembles with the hippocampal local field potential (LFP) is reflected in dynamic calcium activity remains unclear. Here, we recorded hippocampal calcium activity with endoscopic imaging of the genetically encoded fluorophore GCaMP6 with concomitant LFP in freely behaving mice. Dynamic calcium activity was greater in exploratory behavior and REM sleep than in qui… Show more
“…Signal decomposition into aperiodic and periodic components (Donoghue et al, 2020) showed that the optogenetic stimulation enhanced the periodic components with peaks in the theta and slow gamma bands and decreased the aperiodic component of the signal (1/f background). Our observation of the enhanced thetagamma activity might appear at odds with previous reports that such manipulation does not change theta-gamma power during sleep (Ma et al, 2020) and quiet wakefulness (Zhou et al, 2019). The combined effect of the cholinergic stimulation on the periodic and aperiodic signal sums to near-zero values, which could explain the different conclusions, showing the advantage of PSD decomposition (Donoghue et al, 2020) when assessing the power of periodic signals.…”
Section: Cholinergic Influence On Hippocampal Network Activitycontrasting
confidence: 95%
“…Conversely, cholinergic tone and MS cholinergic neuron discharge are at their lowest during slow-wave sleep and wake immobility, which are associated with the highest ripple incidence (Fadda et al, 2000;Ma et al 2020). In accordance with these observations, we found that stimulation of MS cholinergic neurons reduces SWRs both in awake behaving animals and naturally sleeping animals, consistent with previous reports (Figure 4,5;Vandecasteele et al, 2014;Zhou et al, 2019;Ma et al, 2020).…”
Section: Cholinergic Influence On Hippocampal Network Activitysupporting
confidence: 93%
“…In accordance with these observations, we found that stimulation of MS cholinergic neurons strongly reduces ripple activity in both naturally sleeping and anesthetized animals, consistent with previous reports (Figure 3; Vandecasteele et al, 2014;Zhou et al, 2019;Ma et al, 2020). However, MS cholinergic stimulation did not significantly reduce the ripple occurrence in the CA3 when the mouse was in the goal zone of the Y-maze, while the incidence de-creased in the CA1 (Figure 5).…”
Section: Cholinergic Influence On Hippocampal Network Activitysupporting
confidence: 92%
“…We show that stimulation of MS cholinergic neurons promotes theta-gamma rhythm in the CA3 and CA1 of sleeping and anesthetized animals, consistent with previous findings in the CA1 (Figure 4; Vandecasteele et al, 2014;Zhou et al, 2019;Ma et al, 2020). Similar to the report by Vandecasteele et al (2014), only mild effects of MS cholinergic stimulation on theta and gamma peak power were seen in the sleeping mouse (Figure 3) due to a global reduction of the background aperiodic signal (1/f) also observed in Vandecasteele et al (2014).…”
Section: Cholinergic Influence On Hippocampal Network Activitysupporting
confidence: 91%
“…The local release of ACh controls hippocampal network states. In hippocampal CA3, cholinergic activation induces a slow gamma rhythm primarily by activating M1 muscarinic receptors (Fisahn et al, 1998;Betterton et al, 2017), while in the CA1, cholinergic activation promotes theta/gamma oscillations and suppresses ripple oscillations through the activation of M2/M4 muscarinic receptors (Vandecasteele et al, 2014;Zhou et al, 2019;Ma et al, 2020). This suggests that regulation of cholinergic tone allows the switching between online attentive processing (theta/gamma oscillations) and offline memory consolidation (SWRs) as described in the two-stage model of memory trace formation (Buzsaki, 1989).…”
Abbreviated title: Cholinergic modulation of hippocampal memory C o r r e s p o n d i n g a u t h o r e m a i l a d d r e s s : a h 8 3 1 @ c a m . a c . u k , op210@cam.ac.uk Number of pages: 44 Number of figures: 5 + 3 Number of tables: 0 Number of multimedia: 0 Number of 3D models: 0 Number of words for Abstract: 149
“…Signal decomposition into aperiodic and periodic components (Donoghue et al, 2020) showed that the optogenetic stimulation enhanced the periodic components with peaks in the theta and slow gamma bands and decreased the aperiodic component of the signal (1/f background). Our observation of the enhanced thetagamma activity might appear at odds with previous reports that such manipulation does not change theta-gamma power during sleep (Ma et al, 2020) and quiet wakefulness (Zhou et al, 2019). The combined effect of the cholinergic stimulation on the periodic and aperiodic signal sums to near-zero values, which could explain the different conclusions, showing the advantage of PSD decomposition (Donoghue et al, 2020) when assessing the power of periodic signals.…”
Section: Cholinergic Influence On Hippocampal Network Activitycontrasting
confidence: 95%
“…Conversely, cholinergic tone and MS cholinergic neuron discharge are at their lowest during slow-wave sleep and wake immobility, which are associated with the highest ripple incidence (Fadda et al, 2000;Ma et al 2020). In accordance with these observations, we found that stimulation of MS cholinergic neurons reduces SWRs both in awake behaving animals and naturally sleeping animals, consistent with previous reports (Figure 4,5;Vandecasteele et al, 2014;Zhou et al, 2019;Ma et al, 2020).…”
Section: Cholinergic Influence On Hippocampal Network Activitysupporting
confidence: 93%
“…In accordance with these observations, we found that stimulation of MS cholinergic neurons strongly reduces ripple activity in both naturally sleeping and anesthetized animals, consistent with previous reports (Figure 3; Vandecasteele et al, 2014;Zhou et al, 2019;Ma et al, 2020). However, MS cholinergic stimulation did not significantly reduce the ripple occurrence in the CA3 when the mouse was in the goal zone of the Y-maze, while the incidence de-creased in the CA1 (Figure 5).…”
Section: Cholinergic Influence On Hippocampal Network Activitysupporting
confidence: 92%
“…We show that stimulation of MS cholinergic neurons promotes theta-gamma rhythm in the CA3 and CA1 of sleeping and anesthetized animals, consistent with previous findings in the CA1 (Figure 4; Vandecasteele et al, 2014;Zhou et al, 2019;Ma et al, 2020). Similar to the report by Vandecasteele et al (2014), only mild effects of MS cholinergic stimulation on theta and gamma peak power were seen in the sleeping mouse (Figure 3) due to a global reduction of the background aperiodic signal (1/f) also observed in Vandecasteele et al (2014).…”
Section: Cholinergic Influence On Hippocampal Network Activitysupporting
confidence: 91%
“…The local release of ACh controls hippocampal network states. In hippocampal CA3, cholinergic activation induces a slow gamma rhythm primarily by activating M1 muscarinic receptors (Fisahn et al, 1998;Betterton et al, 2017), while in the CA1, cholinergic activation promotes theta/gamma oscillations and suppresses ripple oscillations through the activation of M2/M4 muscarinic receptors (Vandecasteele et al, 2014;Zhou et al, 2019;Ma et al, 2020). This suggests that regulation of cholinergic tone allows the switching between online attentive processing (theta/gamma oscillations) and offline memory consolidation (SWRs) as described in the two-stage model of memory trace formation (Buzsaki, 1989).…”
Abbreviated title: Cholinergic modulation of hippocampal memory C o r r e s p o n d i n g a u t h o r e m a i l a d d r e s s : a h 8 3 1 @ c a m . a c . u k , op210@cam.ac.uk Number of pages: 44 Number of figures: 5 + 3 Number of tables: 0 Number of multimedia: 0 Number of 3D models: 0 Number of words for Abstract: 149
Summary
Dysregulated homeostasis of neural activity has been hypothesized to drive Alzheimer’s disease (AD) pathogenesis. AD begins with a decades-long presymptomatic phase, but whether homeostatic mechanisms already begin failing during this silent phase is unknown. We show that before the onset of memory decline and sleep disturbances, familial AD (fAD) model mice display no deficits in CA1 mean firing rate (MFR) during active wakefulness. However, homeostatic down-regulation of CA1 MFR is disrupted during non-rapid eye movement (NREM) sleep and general anesthesia in fAD mouse models. The resultant hyperexcitability is attenuated by the mitochondrial dihydroorotate dehydrogenase (DHODH) enzyme inhibitor, which tunes MFR toward lower set-point values.
Ex vivo
fAD mutations impair downward MFR homeostasis, resulting in pathological MFR set points in response to anesthetic drug and inhibition blockade. Thus, firing rate dyshomeostasis of hippocampal circuits is masked during active wakefulness but surfaces during low-arousal brain states, representing an early failure of the silent disease stage.
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