Biology subjects

Denis, D.

Publications and source records attributed to Denis, D..

14 recordsLinked to original sources

bioRxiv2026

Gamma-frequency firing persistently enhances intrinsic excitability in retinal ganglion cells

Experience-dependent plasticity is usually attributed to synaptic changes, but neuronal output also depends on changes in intrinsic excitability. Whether intrinsic excitability is persistently modified at the retinal output stage is unknown. Using whole-cell recordings from retinal ganglion cells (RGCs) of juvenile rats, we found that 40-Hz firing produced sustained potentiation of intrinsic excitability in low-input-resistance A-type RGCs and rapid potentiation of intrinsic excitability in high-input-resistance B-type RGCs. In A-type bursting RGCs, long-term potentiation of intrinsic excitability (LTP-IE) required Cav1 calcium channels for its induction. LTP-IE was associated with hyperpolarization of spike threshold and reduction of spike time jitter, due to reduced Kv1 potassium-family channel function. Potentiation also increased the probability that visually-evoked synaptic events triggered action potentials. Patterned firing therefore persistently reconfigures RGC input-output transformation through the Cav1-dependent regulation of Kv1 channels, revealing intrinsic plasticity at the retinal output stage.

neuroscience↗

bioRxiv2026

Homeostatic regulation of intrinsic neuronal excitability in visual thalamic relay cells induced by brief monocular deprivation

Homeostatic plasticity of intrinsic excitability (IE) in the visual system has been essentially shown at the cortical level but whether thalamic nuclei also express homeostatic plasticity of IE is unknown. We show here that 4 days of monocular deprivation (MD) at eye opening induces a homeostatic change in IE in dorsal lateral geniculate nucleus (dLGN) neurons. Neurons recorded in the dLGN region activated by the deprived eye are more excitable than neurons recorded in the dLGN region activated by the open eye. No significant changes were observed following 7 days of MD, however. Enhanced excitability in neurons from the deprived side after 4 days of MD was associated with a reduced Kv1-dependent LTP-IE, a smaller voltage ramp, and a reduced inter-spike interval, suggesting that Kv1 channels are down-regulated in deprived dLGN neurons. Furthermore, the ankyrin G signal of the axon initial segment was larger in deprived dLGN neurons compared with open ones, indicating that Nav1 channel number also undergoes homeostatic regulation, and Kv1.1 channel signals were lower in deprived neurons compared to open ones. In addition, electrical coupling was found to be strengthened in neurons displaying enhanced IE following either brief (4 days) or long (10 days) MD. These results suggest that homeostatic and Hebbian plasticity in the dLGN share common expression mechanisms involving the regulation of Kv1 channels, Nav1 channels and electrical coupling between relay neurons.

neuroscience↗

bioRxiv2026

Vagally Mediated Heart Rate Variability During REM Sleep is Associated with Retention of Fear Extinction in Generalized Anxiety Disorder

Fear extinction processes are central to the pathology and treatment of anxiety disorders. Emerging evidence implicates rapid eye movement (REM) sleep in the consolidation of extinction memory. Separately, converging theory and empirical work suggest that vagally mediated heart rate variability (VmHRV) serves as a peripheral index of cortico-subcortical regulatory capacity relevant to extinction circuitry. On this basis, we tested the hypothesis that VmHRV during REM sleep would be associated with the retention of extinction memory in individuals with generalized anxiety disorder (GAD). Participants underwent a validated two-day fear conditioning and extinction paradigm. Subjective extinction retention (sERI) was quantified during a recall test 24 hours after learning and ambulatory polysomnography was recorded on the intervening night. As hypothesized, higher REM VmHRV was significantly associated with better extinction retention. This association remained robust after controlling psychotropic medication use and REM density. In contrast, VmHRV during SWS or wakefulness, as well as other REM sleep measures, were not associated with extinction retention. These findings identify REM VmHRV as a significant predictor of extinction memory retention in GAD, extending prior findings in trauma-exposed individuals. We propose that reduced vagal tone indexes compromised prefrontal inhibitory control over amygdala and noradrenergic circuits, thereby impairing REM sleep-dependent consolidation. These results position VmHRV during REM sleep as a potential transdiagnostic biomarker of extinction memory processing and suggest that interventions enhancing vagal tone could improve treatment outcomes in anxiety disorders.

neuroscience↗

bioRxiv2025

Slow oscillation-sleep spindle coupling is associated with fear extinction retention in trauma-exposed individuals

Posttraumatic stress disorder (PTSD) can be characterized as a disorder of fear learning and memory, in which there is a failure to retain memory for the extinction of conditioned fear. Sleep has been implicated in successful extinction retention. The coupling of sleep spindles to slow oscillations (SOs) during non-rapid eye movement sleep has been shown to broadly underpin sleeps beneficial effect on memory consolidation. However, the role of this oscillatory coupling in the retention of extinction memories is unknown. In a large sample of 124 trauma-exposed individuals, we investigated SO-spindle coupling in relation to fear extinction memory. We found that participants with a PTSD diagnosis, relative to trauma-exposed controls, showed significantly altered SO-spindle timing, such that PTSD participants exhibited spindle coupling further away from the peak of the SO. Across participants, the amount of coupling significantly predicted extinction retention, with coupled spindles uniquely predicting successful extinction retention compared to uncoupled spindles. These results suggest that SO-spindle coupling is critical for successful retention of extinguished fear, and that SO-spindle coupling dynamics are altered in PTSD. These alterations in the mechanics of sleep may have substantial clinical implications, meriting further investigation.

neuroscience↗

bioRxiv2025

Theta oscillations dictate the evolution of memories across periods of sleep or wakefulness

How does the brain select which experiences to consolidate into long-term memory? Numerous neurobiological frameworks suggest that certain memories are "tagged" at learning for consolidation during later sleep. However, experimental evidence of such a tagging mechanism in the human brain is lacking. Using electroencephalography in humans, we reliably differentiate brain states for memories that are tagged at learning for consolidation across sleep or wakefulness. The tagging of memories for consolidation across sleep (but not wakefulness) was linked to 3-8Hz theta rhythms during learning. The magnitude of this tagging-related theta response predicted the coupling of slow oscillations to sleep spindles during post-learning sleep (an established neural correlate of sleep-dependent memory processing). In turn, slow oscillation-spindle coupling was associated with better memory performance at the post-sleep test. These findings provide new insights into the neural mechanisms through which our brains determine which information is retained for the future.

neuroscience↗

bioRxiv2023

NREM sleep oscillations and their relations with sleep-dependent memory consolidation in early course psychosis and first-degree relatives

Sleep spindles are believed to mediate sleep-dependent memory consolidation, particularly when coupled to neocortical slow oscillations. Schizophrenia is characterized by a deficit in sleep spindles that correlates with reduced overnight memory consolidation. Here, we examined sleep spindle activity, slow oscillation-spindle coupling, and both motor procedural and verbal declarative memory consolidation in early course, minimally medicated psychosis patients and non-psychotic first-degree relatives. Using a four-night experimental procedure, we observed significant deficits in spindle density and amplitude in patients relative to controls that were driven by individuals with schizophrenia. Schizophrenia patients also showed reduced sleep-dependent consolidation of motor procedural memory, which correlated with spindle density. Contrary to expectations, there were no group differences in the consolidation of declarative memory on a word pairs task. Nor did the relatives of patients differ in spindle activity or memory consolidation compared with controls, however increased consistency in the timing of SO-spindle coupling were seen in both patient and relatives. Our results extend prior work by demonstrating correlated deficits in sleep spindles and sleep-dependent motor procedural memory consolidation in early course, minimally medicated patients with schizophrenia, but not in first-degree relatives. This is consistent with other work in suggesting that impaired sleep-dependent memory consolidation has some specificity for schizophrenia and is a core feature rather than reflecting the effects of medication or chronicity. Statement of significanceWe investigated sleep neurophysiology and memory consolidation in minimally-medicated, early course psychosis patients and unaffected first-degree relatives of patients in a four-night study. Early-course schizophrenia patients had a sleep spindle deficit that correlated with reduced procedural memory consolidation. Although first-degree relatives did not show any deficit in spindles or memory consolidation, the spindles of both relatives and patients showed increased consistency of the temporal coupling of spindles with slow oscillations compared with controls. These results suggest that sleep spindle and memory consolidation deficits are a core feature of schizophrenia. Spindle deficits may be a biomarker of schizophrenia modifiable by treatment, and motivate the development of targeted novel interventions.

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bioRxiv2023

Visual activity enhances neuronal excitability in thalamic relay neurons

The dorsal lateral geniculate nucleus (dLGN) has long been held to act as a basic relay for visual information travelling from the retina to cortical areas, but recent findings suggest a largely underestimated functional plasticity of dLGN neurons. However, the cellular mechanisms supporting this functional plasticity have not been yet explored. In particular, it remains to elucidate whether intrinsic neuronal excitability change upon visual stimuli. We show here that monocular deprivation for 10 days reduces the intrinsic excitability of dorsal LGN relay cells. Furthermore, dLGN neurons exhibit long-term potentiation of their intrinsic excitability (LTP-IE) when suprathreshold afferent retinal inputs are stimulated at 40 Hz or when spikes are induced with direct somatic current injection to reproduce patterns of retinal activity. LTP-IE is observed after eye opening and requires calcium influx mediated by L-type calcium channels. It involves activation of PKA and is expressed through the down-regulation of Kv1 potassium channels. In conclusion, our study provides the first evidence for intrinsic plasticity in dLGN relay cells, thus further pointing the role of thalamic neurons in activity-dependent visual plasticity and amblyopia.

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bioRxiv2023

Targeted memory reactivation during non-rapid eye movement sleep enhances neutral, but not negative, components of memory

Emotionally salient components of memory are preferentially remembered at the expense of accompanying neutral information. This emotional memory trade-off is enhanced over time, and possibly sleep, though a process of memory consolidation. Sleep is believed to benefit memory through a process of reactivation during non-rapid eye movement sleep (NREM). Here, targeted memory reactivation (TMR) was used to manipulate the reactivation of negative and neutral memories during NREM sleep. Thirty-one male and female participants encoded scenes containing either a negative or neutral object superimposed on an always neutral background. During NREM sleep, sounds associated with these scenes were replayed, and memory for scene components was tested the following morning. We found that TMR during NREM sleep improved memory for neutral, but not negative scene objects. This effect was associated with sleep spindle activity, with a larger spindle response following TMR cues predicting TMR effectiveness for neutral items only. These findings therefore do not suggest a role of NREM memory reactivation in enhancing the emotional memory trade-off across a 12-hour period but do align with growing evidence of spindle-mediated memory reactivation in service of neutral declarative memory. Significance statementMemory reactivation during sleep is believed to be a key mechanism facilitating consolidation, the strengthening and stabilisation of memories over time. Emotional memories appear to be preferentially consolidated compared to neutral information, but the role sleep-related memory reactivation in this process is still unclear. Here, we found that experimentally reactivating memories during sleep in humans did not preferentially enhance emotional memory components but did improve neutral memory when tested after one night of sleep. These findings speak against a role of memory reactivation in the early stages of memory consolidation.

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bioRxiv2023

Emotional memories are enhanced when reactivated in slow wave sleep, but impaired when reactivated in REM

Sleep supports memory consolidation. However, it is not completely clear how different sleep stages contribute to this process. While rapid eye movement sleep (REM) has traditionally been implicated in the processing of emotionally charged material, recent studies indicate a role for slow wave sleep (SWS) in strengthening emotional memories. Here, to directly examine which sleep stage is primarily involved in emotional memory consolidation, we used targeted memory reactivation (TMR) in REM and SWS during a daytime nap. Contrary to our hypothesis, reactivation of emotional stimuli during REM led to impaired memory. Consistent with this, REM% was correlated with worse recall in the group that took a nap without TMR. Meanwhile, cueing benefit in SWS was strongly correlated with the product of times spent in REM and SWS (SWS-REM product), and reactivation significantly enhanced memory in those with high SWS-REM product. Surprisingly, SWS-REM product was associated with better memory for reactivated items and poorer memory for non-reactivated items, suggesting that sleep both preserved and eliminated emotional memories, depending on whether they were reactivated. Notably, the emotional valence of cued items modulated both sleep spindles and delta/theta power. Finally, we found that emotional memories benefited from TMR more than did neutral ones. Our results suggest that emotional memories decay during REM, unless they are reactivated during prior SWS. Furthermore, we show that active forgetting complements memory consolidation, and both take place across SWS and REM. In addition, our findings expand upon recent evidence indicating a link between sleep spindles and emotional processing.

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bioRxiv2022

Beta spectral power during sleep is associated with impaired recall of extinguished fear

The failure to retain memory for extinguished fear plays a major role in the maintenance of post-traumatic stress disorder (PTSD), with successful extinction recall necessary for symptom reduction. Disturbed sleep, a hallmark symptom of PTSD, impairs fear extinction recall. However, our understanding of the electrophysiological mechanisms underpinning sleeps role in extinction retention remain underdetermined. We examined the relationship between the microarchitecture of sleep and extinction recall in healthy humans (n=46, both male and females included) and a pilot study in individuals with PTSD (n=12). Participants underwent a fear conditioning and extinction protocol over two days, with sleep recording occurring between conditioning and extinction. Twenty-four hours after extinction learning, participants underwent extinction recall. Power spectral density (PSD) was computed for pre- and post-extinction learning sleep. Increased beta band PSD ([~]17-26Hz) during pre-extinction learning sleep was associated with worse extinction recall in healthy participants (r=.41, p=.004). Beta PSD was highly stable across three nights of sleep (intraclass correlations (ICC)>0.92). Individuals with PTSD were found to have increased beta PSD compared to healthy controls (ps < .039), and beta PSD correlated with extinction recall in the PTSD group at a similar magnitude to controls (r=.39). Results suggest beta band PSD is elevated in PTSD, and is specifically implicated in difficulties recalling extinguished fear. Significance statementDisturbed sleep is a hallmark feature of posttraumatic stress disorder (PTSD). Certain neural oscillations that occur during sleep have been shown to be altered in PTSD. These include increased 15-30Hz beta oscillations, which are believed to index cortical hyperarousal. Alongside sleep disturbances, patients also show difficulty in recalling extinguished fear. Although prior studies have linked sleep with extinction retention, no studies have investigated the role that neural oscillations during sleep play in this process. Here, we show in both healthy participants and PTSD patients, that increased beta oscillatory power during sleep is associated with impaired extinction retention. Therefore, this study provides new evidence that electrophysiological changes in the sleep EEG of PTSD patients is also implicated in extinction recall processes.

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bioRxiv2021

Investigation of the Stress and Sleep Physiology Correlates of Next-Day Memory for Details of a Social Stressor Testing Environment

Despite evidence which demonstrates that psychosocial stress interacts with sleep to modulate memory, research that has examined next-day memory for the stressful environment itself has not accounted for post-stressor sleep. Here, participants completed the Trier Social Stress Test or a matched control task with psychophysiological monitoring and stress hormone assays. After a 24-hour delay that included overnight polysomnographically-recorded sleep, memory for objects in the testing room was assessed by having participants draw the testing room from the previous day from memory. As expected, stressed participants mounted greater psychophysiological and stress hormone responses to the stressor than participants in the control condition. However, there was only weak evidence that stress reactivity and post-encoding sleep interacted to modulate memory for testing room details. Instead, NREM sleep physiology on the night following testing room encoding was positively associated with memory for testing room details, though this association occurred in the control, but not stressed, participants.

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bioRxiv2020

Slow oscillation-spindle coupling impairs emotional memory consolidation following stress

Both stress and sleep enhance emotional memory. They also interact, with the largest effect of sleep on emotional memory being seen when stress occurs shortly before or after encoding. Slow wave sleep (SWS) is critical for long-term episodic memory, facilitated by the temporal coupling of slow oscillations and sleep spindles. Prior work in humans has shown these associations for neutral information in non-stressed participants. Whether coupling interacts with stress to facilitate emotional memory formation is unknown. Here, we addressed this question by reanalyzing an existing dataset of 64 individuals. Participants underwent a psychosocial stressor (32) or comparable control (32) prior to the encoding of 150-line drawings of neutral, positive, and negative images. All participants slept overnight with polysomnography, before being given a surprise memory test the following day. In the stress group, time spent in SWS was positively correlated with memory for images of all valences. Results were driven by those who showed a high cortisol response to the stressor, compared to low responders. The amount of slow oscillation-spindle coupling during SWS was negatively associated with neutral and emotional memory in the stress group only. The association with emotional memory was significantly stronger than for neutral memory within the stress group. These results suggest that stress around the time of initial memory formation impacts the relationship between slow wave sleep and memory.

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bioRxiv2020

Using EEG Microstates to Examine Post-Encoding Quiet Rest and Subsequent Word-Pair Memory

Evidence suggests that the brain preferentially consolidates memories during "offline" periods, in which an individual is not performing a task and their attention is otherwise undirected, including spans of quiet, resting wakefulness. Moreover, research has demonstrated that factors such as the initial encoding strength of information influence which memories receive the greatest benefit. Recent studies have begun to investigate these periods of post-learning quiet rest using EEG microstate analysis to observe the electrical dynamics of the brain during these stretches of memory consolidation, specifically finding an increase in the amount of the canonical microstate D during a post-encoding rest period. Here, we implement an exploratory analysis to probe the activity of EEG microstates during a post-encoding session of quiet rest in order to scrutinize the impact of learning on microstate dynamics and to further understand the role these microstates play in the consolidation of memories. We examined 54 subjects (41 female) as they completed a word-pair memory task designed to use repetition to vary the initial encoding strength of the word-pair memories. In this study, we were able to replicate previous research in which there was a significant increase (p < .05) in the amount of microstate D (often associated with the dorsal attention network) during post-encoding rest. This change was accompanied by a significant decrease (p < .05) in the amount of microstate C (often associated with the default mode network). We also found preliminary evidence indicating a positive relationship between the amount of microstate D and improved memory for weakly encoded memories, which merits further exploration.

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bioRxiv2020

Sleep spindles facilitate selective memory consolidation

Sleep has been shown to be critical for memory consolidation, with some research suggesting that certain memories are prioritized for consolidation. Initial strength of a memory appears to be an important boundary condition in determining which memories are consolidated during sleep. However, the role of consolidation-mediating oscillations, such as sleep spindles and slow oscillations, in this preferential consolidation has not been explored. Here, 54 human participants (76% female) studied pairs of words to three distinct encoding strengths, with recall being tested immediately following learning and again six hours later. Thirty-six had a two-hour nap opportunity following learning, whilst the remaining 18 remained awake throughout. Results showed that across six hours awake, weakly encoded memories deteriorated the fastest. In the nap group however, this effect was attenuated, with forgetting rates equivalent across encoding strengths. Within the nap group, consolidation of weakly encoded items was associated with fast sleep spindle density during non-rapid eye movement sleep. Moreover, sleep spindles that were coupled to slow oscillations predicted the consolidation of weak memories independently of uncoupled sleep spindles. These relationships were unique to weakly encoded items, with spindles not correlating with memory for intermediate or strong items. This suggests that sleep spindles facilitate memory consolidation, guided in part by memory strength. Significance statementGiven the countless pieces of information we encode each day, how does the brain select which memories to commit to long-term storage? Sleep is known to aid in memory consolidation, and it appears that certain memories are prioritized to receive this benefit. Here, we found that compared to staying awake, sleep was associated with better memory for weakly encoded information. This suggests that sleep helps attenuate the forgetting of weak memory traces. Fast sleep spindles, a hallmark oscillation of non-rapid eye movement sleep, mediate consolidation processes. We extend this to show that fast spindles were uniquely associated with the consolidation of weakly encoded memories. This provides new evidence for preferential sleep-based consolidation and elucidate a physiological correlate of this benefit.

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