Journal of Neuroscience最新文献

{"title":"A distinct Down-to-Up transition assembly in retrosplenial cortex during slow-wave sleep.","authors":"Ashley N Opalka, Kimberly J Dougherty, Dong V Wang","doi":"10.1523/JNEUROSCI.1484-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1484-24.2025","url":null,"abstract":"<p><p>Understanding the intricate mechanisms underlying slow-wave sleep (SWS) is crucial for deciphering the brain's role in memory consolidation and cognitive functions. It is well-established that cortical delta oscillations (0.5-4 Hz) coordinate communications among cortical, hippocampal, and thalamic regions during SWS. These delta oscillations feature periods of Up and Down states, with the latter previously thought to represent complete cortical silence; however, new evidence suggests that Down states serve important functions for information exchange during memory consolidation. The retrosplenial cortex (RSC) is pivotal for memory consolidation due to its extensive connectivity with memory-associated regions, although it remains unclear how RSC neurons engage in delta-associated consolidation processes. Here, we employed multi-channel in vivo electrophysiology to study RSC neuronal activity in freely behaving male mice during natural SWS. We discovered a discrete assembly of putative excitatory RSC neurons (∼20%) that initiated firing at SWS Down states and reached maximal firing at the Down-to-Up transitions. Therefore, we termed these RSC neurons the Down-to-Up transition Assembly (DUA), and the remaining RSC excitatory neurons as non-DUA. Compared to non-DUA, DUA neurons appear to exhibit higher firing rates, larger cell body size, and lack monosynaptic connectivity with nearby RSC neurons. Furthermore, optogenetics combined with electrophysiology revealed differential innervation of RSC excitatory neurons by memory-associated inputs. Collectively, these findings provide insight into the distinct activity patterns of RSC neuronal subpopulations during sleep and their potential role in memory processes.<b>Significance statement</b> Newly formed memories must undergo memory consolidation, integrating hippocampal-dependent information into pre-existing cortical networks. Recent research highlights a cortical-hippocampal-cortical loop during SWS in this process, indicating the cortex's role in initiating memory consolidation. To investigate how the RSC contributes to SWS and associated consolidation processes, we characterized a novel assembly of RSC neurons that are highly active during SWS Down states, preceding the activity of other RSC neurons during Down-to-Up transitions. We further explored how RSC neurons receive innervation from memory-associated inputs. Our findings shed light on the RSC's role in orchestrating SWS oscillations, revealing a unique assembly of cortical excitatory neurons in potentially promoting SWS Up states.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing tinnitus via inhibitory influence of the sensorimotor system on auditory cortical activity.","authors":"Anne Sabados, Cora Kim, Stefan Rampp, Elisabeth Bergherr, Michael Buchfelder, Oliver Schnell, Nadia Müller-Voggel","doi":"10.1523/JNEUROSCI.0581-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0581-24.2025","url":null,"abstract":"<p><p>Tinnitus is the subjective perception of a sound in absence of corresponding external acoustic stimuli. Research highlights the influence of the sensorimotor system on tinnitus perception. Associated neuronal processes, however, are insufficiently understood and it remains unclear how and at which hierarchical level the sensorimotor system interacts with the tinnitus-processing auditory system. We therefore asked 23 patients suffering from chronic tinnitus (11 males) to perform specific exercises, aimed at relaxing or tensing the jaw area, which temporarily modulated tinnitus perception. Associated neuronal processes were assessed using Magnetencephalography. Results show that chronic tinnitus patients experienced their tinnitus as weaker and less annoying after completion of relaxing compared to tensing exercises. Furthermore, (1) sensorimotor alpha power and alpha-band connectivity directed from the somatosensory to the auditory cortex increased, and (2) gamma power in the auditory cortex, reduced, which (3) related to reduced tinnitus annoyance perception on a trial-by-trial basis in the relaxed state. No effects were revealed for 23 control participants without tinnitus (6 males) performing the same experiment. We conclude that the increase in directed alpha-band connectivity from somatosensory to auditory cortex is most likely reflecting the transmission of inhibition from somatosensory to auditory cortex during relaxation, where concurrently tinnitus-related gamma power reduces. We suggest that revealed neuronal processes are transferable to other tinnitus modulating systems beyond the sensorimotor one that are e.g. involved in attentional or emotional tinnitus modulation and provide deeper mechanistic insights into how and through which channels phantom sound perception might be modulated on a neuronal level.<b>Significance Statement</b> Tinnitus describes the perception of auditory phantom sounds. Research suggests that the sensorimotor system impacts on tinnitus perception, associated neuronal mechanisms, however, have remained unclear. Here, chronic tinnitus patients performed exercises with the jaw temporarily reducing (versus increasing) tinnitus perception. Tinnitus reduction was accompanied by an increase of alpha-band connectivity directed from the somatosensory to the auditory cortex and gamma power reduction in the auditory cortex. We suggest that the increase in alpha-band connectivity, when tinnitus is reduced, reflects the transmission of inhibition from somatosensory to auditory cortex, where, in parallel, probably tinnitus-related, gamma power reduces. The findings have important implications both for the understanding of phantom sound perception and, more generally, of top-down modulation in healthy and impaired cognition.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Modulation of Low-frequency Cardiac Rhythms on Resting-state Left Insula Alpha Oscillations in Major Depressive Disorder: Evidence from A Magnetoencephalography Study.","authors":"Qian Liao, Zhongpeng Dai, Cong Pei, Han Zhang, Lingling Hua, Hongliang Zhou, Junling Sheng, Zhijian Yao, Qing Lu","doi":"10.1523/JNEUROSCI.1327-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1327-24.2025","url":null,"abstract":"<p><p>A growing body of evidence suggests that the link between the cardiac autonomic nervous system (ANS) and the central nervous system (CNS) is crucial to the onset and development of major depressive disorder (MDD), affecting perception, cognition, and emotional processing. The bottom-up heart-brain communication pathway plays a significant role in this process. Previous studies have shown that slow-frequency oscillations of peripheral signals (e.g., respiration, stomach) can influence faster neural activities in the CNS via phase-amplitude coupling (PAC). However, the understanding of heart-brain coupling remains limited. Additionally, while MDD patients exhibit altered brain activity patterns, little is known about how heart rate variability (HRV) affects brain oscillations. Therefore, we used PAC to investigate heart-brain coupling and its association with depression. We recorded MEG and ECG data from 55 MDD patients (35 females) and 52 healthy subjects (28 females) at rest and evaluated heart-brain PAC at a broad-band level. The results showed that the low-frequency component of HRV (HRV-LF) significantly modulated MEG alpha power (10 Hz) in humans. Compared to the healthy group, the MDD group exhibited more extensive heart-brain coupling cortical networks, including the pars triangularis. LF-alpha coupling was observed in the bilateral insula in both groups. Notably, results revealed a significantly increased sympathetic-dominated HRV-LF modulation effect on left insula alpha oscillations, along with increased depressive severity. These findings suggest that MDD patients may attempt to regulate their internal state through enhanced heart-brain modulation, striving to restore normal physiological and psychological balance.<b>Significance Statement</b> The afferent pathway from the heart plays a pivotal role in conveying information to the brain. This process involves the transmission of signals related to the physiological state of the heart. Our understanding of this pathway and its association with major depressive disorders (MDD) remains limited. In this study, the low-frequency component of heart rate variability (HRV-LF) was found to modulate neural activity during rest, revealing a bottom-up information transmission mechanism between the cardiac ANS and the CNS. Alterations in the LF-alpha coupling pattern were observed in patients with MDD, suggesting this as a potential neurobiological mechanism behind their altered interoception, which might affect the perception and emotional processing.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distributed intracranial activity underlying human decision-making behavior.","authors":"Jacqueline A Overton, Karen A Moxon, Matthew P Stickle, Logan M Peters, Jack J Lin, Edward F Chang, Robert T Knight, Ming Hsu, Ignacio Saez","doi":"10.1523/JNEUROSCI.0572-24.2024","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0572-24.2024","url":null,"abstract":"<p><p>Value-based decision-making involves multiple cortical and subcortical brain areas, but the distributed nature of neurophysiological activity underlying economic choices in the human brain remains largely unexplored. Specifically, the nature of the neurophysiological representation of reward-guided choices, as well as whether they are represented in a subset of reward-related regions or in a more distributed fashion is unknown. Here, we hypothesize that reward choices, as well as choice-related computations (win probability, risk), are primarily represented in high-frequency neural activity reflecting local cortical processing, and that they are highly distributed throughout the human brain, engaging multiple brain regions. To test these hypotheses, we used intracranial recordings from multiple areas (including orbitofrontal, lateral prefrontal, parietal, cingulate cortices as well as subcortical regions such as the hippocampus and amygdala) from neurosurgical patients of both sexes playing a decision-making game. We show that high frequency activity (gamma and high-frequency activity) represents both individual choice-related computations (e.g., risk, win probability) and choice information with different prevalence and regional representation. Choice-related computations are locally and unevenly present in multiple brain regions, whereas choice information is widely distributed, more prevalent, and appears later across all regions examined. These results suggest brain-wide reward processing, with local high frequency activity reflecting the coalescence of choice-related information into a final choice, and shed light on the distributed nature of neural activity underlying economic choices in the human brain.<b>Significance Statement</b> Economic decision-making depends on multiple brain areas. However, how neural activity in the human brain supports choices is not well understood, due to the difficulty of measuring human neural activity. Here, we leveraged the rare opportunity to record electrophysiological activity from several human brain regions implicated in decision-making from neurosurgical patients to study the neurophysiological basis of economic decisions. We show that neural activity supporting human economic choices under uncertainty is highly distributed across brain areas. However, different relevant calculations, such as the probability of a win, or the risk of an uncertain choice, are differentially reflected in across brain regions. This study demonstrates the highly distributed, but regionally specific, nature of choices and reward computations in the human brain.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of striatum in controlling waiting during reactive and self-timed behaviors.","authors":"Qiang Zheng, Yujing Liu, Yue Huang, Jiaming Cao, Xuanning Wang, Jianing Yu","doi":"10.1523/JNEUROSCI.1820-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1820-24.2025","url":null,"abstract":"<p><p>The ability to wait before responding is crucial for many cognitive functions, including reaction time tasks, where one must resist premature actions before the stimulus and respond quickly once the stimulus is presented. However, the brain regions governing waiting remain unclear. Using localized excitotoxic lesions, we investigated the roles of the motor cortex (MO) and sensorimotor dorsolateral striatum (DLS) in male rats performing a conditioned lever release task with variable delays. Neural activity in both MO and DLS showed similar firing patterns during waiting and responding periods. However, only bilateral DLS lesions caused a sustained increase in premature (anticipatory) responses, whereas bilateral MO lesions primarily prolonged reaction times. In a self-timing version of the task, where rats held a lever for a fixed delay before release, DLS lesions caused a leftward shift in response timing, leading to persistently greater premature responses. These waiting deficits were accompanied by reduced motor vigor, such as slower reward-orienting locomotion. Our findings underscore the critical role of the sensorimotor striatum in regulating waiting behavior in timing-related behaviors.<b>Significant Statement</b> Waiting is essential for the temporal control of actions, as many cognitive behaviors-whether stimulus-driven or internally planned-require withholding a response until the appropriate time. However, the neural substrates of waiting remain less understood. Using targeted lesions, we identified the dorsolateral striatum as a crucial region for waiting in both reaction time and self-timing tasks. Lesions in this area caused a persistent increase in premature responses across tasks. In contrast, motor cortex lesions, despite its neurons showing similar activity patterns to the striatum during waiting, did not result in a lasting increase in premature responses; instead, they led to a long-term increase in reaction time.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memory boost for recurring emotional events is driven by initial amygdala response promoting stable neocortical patterns across repetitions.","authors":"Valentina Krenz, Arjen Alink, Benno Roozendaal, Tobias Sommer, Lars Schwabe","doi":"10.1523/JNEUROSCI.2406-23.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.2406-23.2025","url":null,"abstract":"<p><p>Emotionally arousing events are typically vividly remembered, which is generally adaptive but may contribute to mental disorders such as posttraumatic stress disorder. Previous research on emotional memory focused primarily on events that were experienced only once, leaving the memory mechanisms underlying repeatedly encountered emotional events largely unexplored. Here, we aimed to elucidate the brain mechanisms associated with memory for recurring emotional events. Specifically, we sought to determine whether the memory enhancement for recurring emotional events is linked to more variable neural representations, as predicted by the encoding-variability hypothesis, or to more stable representations across repetitions, as suggested by a memory reinstatement account. To investigate this, healthy men and women were repeatedly presented with images of emotionally negative or neutral scenes during three consecutive runs in an MRI scanner. Subsequent free recall was, as expected, enhanced for emotional compared to neutral images. Neural data showed that this emotional enhancement of memory was linked to (i) activation of the amygdala and anterior hippocampus during the initial encounter of the emotional event and (ii) increased neural pattern similarity in frontoparietal cortices across event repetitions. Most importantly, a multilevel moderated mediation analysis revealed that the impact of neocortical pattern stability across repetitions on emotional memory enhancement was moderated by amygdala activity during the initial exposure to the emotional event. Together, our findings show that the amygdala response during the initial encounter of an emotional event boosts subsequent remembering through a more precise reinstatement of the event representation during subsequent encounters of the same event.<b>Significance statement</b> Despite extensive research on emotional memory, the mechanisms underlying memory formation for recurrent emotional events remain elusive. We show that amygdala and anterior hippocampal activity is most prominent during the initial exposure to an aversive stimulus and decreases markedly with repeated exposure. Neocortical representation patterns of subsequently recalled emotional events, however, are more stable across the repeated encounters of emotional (vs. neutral) events, in line with a memory reinstatement account. Notably, this increased neocortical pattern stability was driven by the amygdala response during the initial exposure to an emotional event. These findings provide novel insights into the mechanisms involved in memory formation for recurrent emotional events, with potential implications for complex post-traumatic stress disorder characterized by multiple traumatic exposures.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Serotonergic Dorsal Raphe Promotes Emergence from Propofol Anesthesia in Zebrafish.","authors":"Xiaoxuan Yang, Shan Zhu, Miaoyun Xia, Le Sun, Sha Li, Peishan Xiang, Funing Li, Qiusui Deng, Lijun Chen, Wei Zhang, Ying Wang, Qiang Li, Zhuochen Lyu, Xufei Du, Jiulin Du, Qianzi Yang, Yan Luo","doi":"10.1523/JNEUROSCI.2125-23.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.2125-23.2025","url":null,"abstract":"<p><p>The mechanisms through which general anesthetics induce loss of consciousness remain unclear. Previous studies have suggested that dorsal raphe nucleus serotonergic (DRN^5-HT) neurons are involved in inhalational anesthesia, but the underlying neuronal and synaptic mechanisms are not well understood. In this study, we investigated the role of DRN^5-HT neurons in propofol-induced anesthesia in larval zebrafish (sex undetermined at this developmental stage) using a combination of in vivo single-cell calcium imaging, two-photon laser ablation, optogenetic activation, in vivo glutamate imaging and in vivo whole-cell recording. We found that calcium activity of DRN^5-HT neurons reversibly decreased during propofol perfusion. Ablation of DRN^5-HT neurons prolonged emergence from 30 μM propofol anesthesia, while induction times were not affected under concentrations of 1 μM, 3 μM, and 30 μM. Additionally, optogenetic activation of DRN^5-HT neurons strongly promoted emergence from propofol anesthesia. Propofol application to DRN^5-HT neurons suppressed both spontaneous and current injection-evoked spike firing, abolished spontaneous excitatory postsynaptic currents, and decreased membrane input resistance. Presynaptic glutamate release events in DRN^5-HT neurons were also abolished by propofol. Furthermore, the hyperpolarization of DRN^5-HT neurons caused by propofol was abolished by picrotoxin, a GABA_A receptor antagonist, which shortened emergence time from propofol anesthesia when locally applied to the DRN. Our results reveal that DRN^5-HT neurons in zebrafish are involved in the emergence from propofol anesthesia by inhibiting presynaptic excitatory glutamate inputs and inducing GABA_A receptor-mediated hyperpolarization.<b>Significance Statement</b> The neural mechanisms of general anesthesia remain unclear. We studied the role of the dorsal raphe nucleus serotonergic (DRN^5-HT) neurons in propofol anesthesia using larval zebrafish, employing in vivo calcium imaging at single-neuron resolution, two-photon ablation, optogenetic activation, and in vivo whole-cell recording. We found that the DRN^5-HT neurons are involved in emergence from anesthesia, but not induction. Propofol suppresses DRN^5-HT activity by inhibiting the activity of DRN^5-HT neurons via GABA_A receptors and blocking presynaptic excitatory glutamate inputs. These findings further support larval zebrafish as an ideal model for investigating the mechanisms of general anesthesia.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimulus-dependent expression of <i>Bdnf</i> is mediated by ATF2, MYT1L, and EGR1 transcription factors.","authors":"Eli-Eelika Esvald, Andra Moistus, Karin Lehe, Annela Avarlaid, Anastassia Šubina, Liis Kuusemets, Jürgen Tuvikene, Tõnis Timmusk","doi":"10.1523/JNEUROSCI.0313-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0313-24.2025","url":null,"abstract":"<p><p>Neurotrophins like BDNF have a key role in the proper functioning of the central nervous system, influencing numerous processes like memory formation and behavior. An imbalance in BDNF levels can lead to a wide range of diseases, including depression and neurodevelopmental disorders. While the potential therapeutic effects of BDNF are well-recognized, there is a knowledge gap in understanding the mechanisms governing BDNF expression levels. Here, we focused on the regulation of <i>Bdnf</i> gene expression in response to different stimuli, specifically studying the effects of neuronal activity and BDNF-TrkB signaling on <i>Bdnf</i> transcription in cultured neurons from rats of either sex. We used <i>in vitro</i> DNA pulldown combined with mass spectrometry to determine transcription factors that interact with the <i>Bdnf</i> promoters upon different stimuli and validated numerous known regulators, such as USF and AP1 family, and novel candidate regulators using reporter assays. We show that the USF family of transcription factors is specifically recruited after membrane depolarization, whereas the AP1 family participates in <i>Bdnf</i> regulation only after BDNF-TrkB signaling. We further describe ATF2, MYT1L and EGR family as novel regulators of <i>Bdnf</i> expression by demonstrating their direct binding to <i>Bdnf</i> promoters using chromatin immunoprecipitation assays both <i>in vitro</i> and in vivo, showing their functional role in <i>Bdnf</i> gene expression, and ultimately identifying their regulatory <i>cis</i>-elements in <i>Bdnf</i> promoters. Furthermore, our results show competition between ATF2, CREB, and AP1 family in regulating <i>Bdnf</i> levels. Collectively, our results provide insight into the regulation of <i>Bdnf</i> expression upon different stimuli.<b>Significance statement</b> Membrane depolarization and neurotrophin BDNF (brain-derived neurotrophic factor) signaling via its receptor TrkB (tropomyosin receptor kinase B) are critical processes for proper neuronal functions. Here, we studied how these two stimuli regulate the expression of two main <i>Bdnf</i> transcripts - <i>Bdnf</i> exon I- and IV-containing transcripts. Our results reveal a remarkable overlap of regulators that are recruited to both <i>Bdnf</i> promoters I and IV and after both stimuli. Overall, our results shed light to the complex regulation of <i>Bdnf</i> expression highlighting a dynamic interplay of cooperative and competitive mechanisms among transcription factors. Understanding the regulatory mechanisms beyond single transcription factors and considering the combinatorial effects could pave the way for specifically modulating <i>Bdnf</i> levels as therapeutic interventions.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurophysiology of perceptual decision-making and its alterations in attention-deficit hyperactivity disorder (ADHD).","authors":"Mana Biabani, Kevin Walsh, Shou-Han Zhou, Joseph Wagner, Alexandra Johnstone, Julia Paterson, Natasha Matthews, Beth P Johnson, Gerard M Loughnane, Redmond G O'Connell, Mark A Bellgrove","doi":"10.1523/JNEUROSCI.0469-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0469-24.2025","url":null,"abstract":"<p><p>Despite the prevalence of ADHD, efforts to develop a detailed understanding of the neuropsychology of this neurodevelopmental condition are complicated by the diversity of interindividual presentations and the inability of current clinical tests to distinguish between its sensory, attentional, arousal or motoric contributions. Identifying objective methods that can explain the diverse performance profiles across individuals diagnosed with ADHD has been a long-held goal. Achieving this could significantly advance our understanding of etiological processes and potentially inform the development of personalized treatment approaches. Here, we examine key neuropsychological components of ADHD within an electrophysiological (EEG) perceptual decision-making paradigm that is capable of isolating distinct neural signals of several key information processing stages necessary for sensory-guided actions from attentional selection to motor responses. Using a perceptual decision-making task (random dot motion), we evaluated the performance of 79 children (aged 8 to 17 years) and found slower and less accurate responses, along with a reduced rate of evidence accumulation (drift rate parameter of drift diffusion model), in children with ADHD (n = 37; 13 female) compared to typically developing peers (n = 42; 18 female). This was driven by the atypical dynamics of discrete electrophysiological signatures of attentional selection, the accumulation of sensory evidence, and strategic adjustments reflecting urgency of response. These findings offer an integrated account of decision-making in ADHD and establish discrete neural signals that might be used to understand the wide range of neuropsychological performance variations in individuals with ADHD.<b>Significance Statement</b> The efficacy of diagnostic and therapeutic pathways in ADHD is limited by our incomplete understanding of its neurological basis. One promising avenue of research is the search for basic neural mechanisms that may contribute to the variety of cognitive challenges associated with ADHD. We developed a mechanistic account of differences in a fundamental cognitive process by integrating across neurocognitive, neurophysiological (i.e., EEG), and computational levels of analysis. We detected distinct neural changes in ADHD that explained altered performance (e.g., slowed and less accurate responses). These included changes in neural patterns of attentional selection, sensory information processing, and response preparation. These findings enhance our understanding of the neurophysiological profile of ADHD and may offer potential targets for more effective, personalized interventions.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life stress impairs VTA coordination of BLA network and behavioral states.","authors":"Bradly T Stone, Pantelis Antonoudiou, Eric Teboul, Garrett Scarpa, Grant Weiss, Jamie L Maguire","doi":"10.1523/JNEUROSCI.0088-24.2025","DOIUrl":"10.1523/JNEUROSCI.0088-24.2025","url":null,"abstract":"<p><p>Motivated behaviors, such as social interactions, are governed by the interplay between mesocorticolimbic structures, such as the ventral tegmental area (VTA), basolateral amygdala (BLA), and medial prefrontal cortex (mPFC). Adverse childhood experiences and early life stress (ELS) can impact these networks and behaviors, which is associated with increased risk for psychiatric illnesses. While it is known that the VTA projects to both the BLA and mPFC, the influence of these inputs on local network activity which govern behavioral states - and whether ELS impacts VTA-mediated network communication - remains unknown. Our study demonstrates that VTA inputs influence BLA oscillations and entrainment of mPFC activity in mice, and that ELS weakens the ability of the VTA to coordinate BLA network states, while also impairing dopaminergic signaling between VTA and BLA. Optogenetic stimulation of VTA_BLA terminals decreased social interaction in ELS mice, which can be recapitulated in control mice by inhibiting VTA-BLA communication. These data suggest that ELS impacts social reward via the VTA-BLA dopamine network.<b>Significance Statement</b> It is well established that oscillatory states in the basolateral amygdala (BLA) govern behavioral states. However, a gap in our knowledge exists regarding the mechanisms mediating transitions between BLA network states. Here we demonstrate a novel mechanism modulating BLA network states involving dopamine inputs from the VTA. Further, we demonstrate that early life stress, a major risk factor for psychiatric illnesses, impairs the ability of dopaminergic inputs from the VTA to coordinate BLA and mPFC network states. Thus, this study provides a novel mechanism mediating transitions between oscillatory states in the BLA which are well documented to govern behavioral states and demonstrates pathological perturbations in the ability of the VTA to coordinate BLA network states following early life stress.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}