Journal of neurophysiology最新文献

{"title":"The effects of medial gastrocnemius muscle fatigue on regional modulation of the ankle plantarflexors during standing external perturbations.","authors":"Nicole D Grzywnowicz, Tanya D Ivanova, S Jayne Garland","doi":"10.1152/jn.00159.2025","DOIUrl":"10.1152/jn.00159.2025","url":null,"abstract":"<p><p>The ankle plantarflexor muscles [medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SOL)] were shown to exhibit direction-specific regional modulation of muscle activity during external perturbations. This study investigated the effect of MG muscle fatigue on plantarflexor muscle activation patterns. It was hypothesized that fatigue of MG would be compensated for by changing the activity of the SOL and LG to maintain balance. Using external perturbations of 1% body mass, the unipedal standing balance of 20 volunteers was tested before and after low-frequency fatigue was induced in MG via electrical stimulation. High-density surface electromyography (HDsEMG) was used to determine the amplitude and barycenter location of the muscle activation in three perturbation directions: 0° (front), 60° left of front (60 L), 60° right of front (60 R). Kinetic analysis was used to evaluate the center of pressure (COP) displacements. Two-way repeated measures ANOVA showed that prefatigue, the HDsEMG amplitude, and barycenter of MG and LG were regionally modulated with perturbation direction (<i>P</i> < 0.01 for both parameters and muscles), whereas in SOL, only the barycenter location modulated across the perturbation direction (<i>P</i> < 0.01). Following MG fatigue, there was no observed difference in MG barycenter location across perturbation directions, and MG amplitude increased only in the front direction. Both LG and SOL maintained the regional muscle activation patterns across perturbation directions (<i>P</i> < 0.01 for both), and the HDsEMG amplitude increased only in LG (<i>P</i> < 0.001). Therefore, MG fatigue resulted in loss of regional activation in MG but did not affect regional activation in the unfatigued plantarflexors.<b>NEW & NOTEWORTHY</b> Regional modulation of electromyography (EMG) with perturbation direction within each plantarflexor (evidenced by the EMG barycenter shift) was lost in fatigued medial gastrocnemius (MG) but was maintained in unfatigued synergists. Regional modulation of EMG following directional perturbations was associated with center of pressure (COP) displacement, reinforcing that the shift in EMG barycenter was serving to oppose the perturbation. Responses to directional perturbations helped counteract low-frequency fatigue of MG by decreasing postural sway and increasing EMG amplitude in both MG and lateral gastrocnemius (LG).</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"382-396"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced amygdala inhibitory neurotransmission and its vulnerability to hyperthermic stress in <i>Atp1a2</i>-deficient heterozygous mice.","authors":"Shin'Ichiro Satake, Shigefumi Yokota, Keiko Ikeda","doi":"10.1152/jn.00157.2025","DOIUrl":"10.1152/jn.00157.2025","url":null,"abstract":"<p><p>The sodium pump (Na,K-ATPase, NKA) is a membrane-bound enzyme crucial for maintaining Na⁺/K⁺ electrochemical gradients across plasma membranes. NKA constitutes catalytic α and auxiliary β subunits, of which four α and three β isoforms have been identified. The physiological roles of the isoforms are not fully understood; nevertheless, mutations in the human α2 subunit gene <i>ATP1A2</i> have been linked to various neurological disorders, including familial hemiplegic migraine type 2 (FHM2), alternating hemiplegia of childhood (AHC), and epilepsy syndromes, with symptoms typically triggered by physical and psychological stressors. Mice lacking <i>Atp1a2</i> die of respiratory failure at birth, whereas heterozygous fetuses (<i>Atp1a2</i>^+/-) survive and exhibit increased c-Fos expression in the principal excitatory neurons of the amygdala, suggesting increased neuronal activity. We compared neurotransmission properties in the basolateral amygdala (BLA) between juvenile <i>Atp1a2</i>^+/- mice and their wild-type (WT) littermates using acute brain slices to elucidate the physiological significance of α2-NKA. Focal electrical stimulation elicited inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs) in regularly spiking principal neurons within the BLA. Both IPSC and EPSC amplitudes increased linearly with stimulation intensity. IPSCs were consistently larger in <i>Atp1a2</i>^+/- than in WT, whereas EPSCs were comparable between the two groups. Notably, the enhanced inhibitory neurotransmission observed in <i>Atp1a2</i>^+/- was abolished under hyperthermic stress. The disrupted balance between inhibition and excitation in BLA neuronal networks may be a key pathophysiological mechanism underlying α2-NKA-related disorders.<b>NEW & NOTEWORTHY</b> The study findings indicated an enhancement of inhibitory synaptic transmission in the developing amygdala of <i>Atp1a2</i>-deficient heterozygous mice, with hyperthermic stress disrupting this enhanced inhibition. Synaptic imbalances in the amygdala circuit likely contribute to the pathophysiology of neurological disorders associated with NKA α2 subunit dysfunction. These findings enhance our understanding of <i>Atp1a2</i>-related diseases and may introduce novel avenues for exploring the mechanisms by which physical stressors exacerbate these conditions.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"216-228"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biocide mixture (CMIT/MIT) induces neurotoxicity through the upregulation of the MAPKs signaling pathways.","authors":"Francesco Molinari, Nicla Tranchida, Francesca Inferrera, Roberta Fusco, Caterina Faggio, Federica Impellitteri, Salvatore Cuzzocrea, Marika Cordaro, Rosanna Di Paola","doi":"10.1152/jn.00104.2025","DOIUrl":"10.1152/jn.00104.2025","url":null,"abstract":"<p><p>The biocides 5-chloro-2-methyl-2h-isothiazolin-3-one and 2-methyl-2h-isothiazolin-3-one (CMIT/MIT) are widely used and can be found in many different types of water-soluble consumer products, such as shampoo, dentifrice, and germicide. Recent reports have suggested that it may be harmful to the skin and lungs. Although not known to be linked to pathogenic cellular and molecular pathways, it is a recognized risk factor for endangering public health. Therefore, the aim of this study was to examine the impact of CMIT/MIT (in 3:1 ratio) in SH-SY5Y human neuroblastoma cells. SHSY-5Y cells were exposed to different concentration (0, 12.5, 25, and 50 μM) of CMIT/MIT for 24 h. Cellular proliferation was considerably reduced in the MTT assay after CMIT/MIT exposure. In addition, the results showed an increase in lactate dehydrogenase (LDH) release and lipid peroxidation and a decrease in physiological antioxidant defense. We also observed an activation of Nrf-2/HO-1 signaling pathway by Western blot and qRT-PCR. Exposure to CMIT/MIT (in 3:1 ratio) also increased the release of proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α. Furthermore, in SHSY-5Y, CMIT/MIT (in 3:1 ratio) raised the levels of phosphorylated ERK1/2, phosphorylated p38, and phosphorylated JNK1/2 proteins. The activation of these pathways was strongly connected with the cell cycle-related genes p53 and p21 and the activation of apoptotic cascade. These results imply that the Nrf-2/HO-1, p38-JNK1/2-ERK1/2, and Bax/Bcl-2 signaling pathways are responsible for inducing cellular damage and accelerating neuronal aging in response to CMIT/MIT (in 3:1 ratio) exposure.<b>NEW & NOTEWORTHY</b> 5-Chloro-2-methyl-2h-isothiazolin-3-one and 2-methyl-2h-isothiazolin-3-one (CMIT/MIT) are widely used, but they may be harmful to the skin and lungs. CMIT/MIT reduces cell viability and induces lactate dehydrogenase (LDH) release in SHSY5Y cell line. CMIT/MIT induces oxidative stress, lipid peroxidation, and activates endogenous antioxidant system. CMIT/MIT induces proinflammatory cytokines release. CMIT/MIT promoted the upregulation of MAPKs and induces apoptosis.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"183-192"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic inflammatory pain and chronic THC vapor inhalation alter midbrain neuronal activity.","authors":"Leslie K Kelley, Nicholas W Gilpin, Jason W Middleton","doi":"10.1152/jn.00456.2024","DOIUrl":"10.1152/jn.00456.2024","url":null,"abstract":"<p><p>In an effort to reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain. We tested chronic delta-9 tetrahydrocannabinol (THC) vapor inhalation effects on intrinsic and synaptic properties of ventrolateral periaqueductal gray (vlPAG) neurons in male and female rats treated with complete Freund's adjuvant (CFA). We report that chronic THC vapor inhalation modulates intrinsic and synaptic properties of vlPAG neurons, including reductions in action potential firing rate and spontaneous inhibitory synaptic transmission in males, and that these effects occur specifically in neurons that respond to current input with a \"delayed\" firing phenotype. Treatment with CFA led to increased firing rate and increased spontaneous inhibitory postsynaptic current (sIPSC) amplitude in vlPAG neurons of female rats, and chronic THC vapor rescued sIPSC amplitudes to control levels-these effects in females were specific to vlPAG neurons categorized as having an \"onset\" firing phenotype. Ongoing work is exploring sex-specific mechanisms and cell types involved in THC vapor inhalation effects on vlPAG neurons in rats treated with CFA, and determining the role of these changes in THC vapor inhalation effects on pain-related behavior.<b>NEW & NOTEWORTHY</b> Many in the United States with pain self-medicate with delta-9 tetrahydrocannabinol (THC) and cannabis, and many humans use e-cigarette-type devices filled with cannabis extracts to self-administer THC. Until recently, most rodent studies have used injection procedures and male rats. Chronic THC vapor reduced synaptic inhibition and neural firing in ventrolateral periaqueductal gray (vlPAG) neurons in males and rescued chronic inflammatory pain-induced increase in synaptic inhibition in females.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"80-93"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experience-induced NPAS4 reduces dendritic inhibition from CCK+ inhibitory neurons and enhances plasticity.","authors":"Daniel A Heinz, Wenhao Cui, Kimberly L Cooper, Brenda L Bloodgood","doi":"10.1152/jn.00216.2025","DOIUrl":"10.1152/jn.00216.2025","url":null,"abstract":"<p><p>Flexibility of neurological systems stems from a host of biological responses to changing experience. When a mouse explores an enriched environment, neurons throughout the brain express the inducible transcription factor NPAS4. In CA1 of the hippocampus, pyramidal neurons that express NPAS4 receive more perisomatic inhibition from cholecystokinin (CCK+) inhibitory neurons and less dendritic inhibition from a previously unidentified inhibitory neuron population. Here, we show that this reduction in dendritic inhibition is specific to synapses made by CCK+ inhibitory neurons and that these NPAS4-dependent changes result in facilitation of theta-burst synaptic plasticity. Thus, NPAS4 expression reorganizes inhibition from a genetically defined population of inhibitory neurons, changing learning rules in response to an animal's interactions with its environment.<b>NEW & NOTEWORTHY</b> How does an inducible transcription factor affect neuronal and circuit function? Here we show that housing mice in an enriched environment induces NPAS4 expression in CA1 pyramidal neurons, leading to a reduction in dendritic inhibition specifically from cholecystokinin (CCK+) inhibitory neurons. This facilitates excitatory synaptic plasticity, indicating a potential mechanistic link between environmental enrichment and enhanced cognitive flexibility.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"361-371"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and implications of high depolarization baseline offsets in conductance-based neuronal models.","authors":"Anal Kumar, Anzal K Shahul, Upinder S Bhalla","doi":"10.1152/jn.00617.2024","DOIUrl":"10.1152/jn.00617.2024","url":null,"abstract":"<p><p>Somatic step-current injection is commonly used to characterize the electrophysiological properties of neurons. Many neuronal types show a large depolarization baseline offset (DBLO), which is defined as the positive difference between the minimum membrane potential during action potential trains and resting. We used stochastic parameter search in experimentally constrained conductance-based models to show that four key factors together account for high DBLO: liquid junction potential correction, high backpropagating passive charges during the repolarization phase of an action potential, fast potassium delayed rectifier kinetics, and appropriate transient sodium current kinetics. Several plausible mechanisms for DBLO, such as Ohmic depolarization due to current input or low-pass filtering by the membrane, fail to explain the effect, and many published conductance-based models do not correctly manifest high DBLO. Finally, physiological levels of DBLO constrain ion channel levels and kinetics, and are linked to cellular processes such as bistable firing, spikelets, and calcium influx.<b>NEW & NOTEWORTHY</b> Our study uncovers mechanisms behind a poorly understood phenomenon-the high membrane potential baseline during depolarization-induced action potential trains. Using data-driven conductance-based pyramidal neuron models, we identify somatic-dendritic electrotonic coupling, potassium channel deactivation kinetics, and sodium channel kinetics as key contributors. We show that ignoring high depolarization baseline leads to incorrect predictions about ion channel levels and neuronal computations. The insights gained from this work will enable more accurate and precise neuronal modeling.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"20-45"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating motor unit firing rates during arm cycling compared with intensity-matched isometric contractions in humans.","authors":"Daniel C Basile, Alysha D Wira, Charles L Rice, Kevin E Power","doi":"10.1152/jn.00128.2025","DOIUrl":"10.1152/jn.00128.2025","url":null,"abstract":"<p><p>Studies in humans have not assessed motor unit firing rates (MUFRs) recorded from intramuscular electromyography (EMG) during a rhythmic locomotor output. Using arm cycling as a model of locomotor-generated activity, the purpose was to determine whether MUFRs differed during arm cycling compared with intensity-matched isometric contractions. We hypothesized that MUFRs would be greater during arm cycling than isometric contractions, assessed at various working intensities. Young males (<i>n</i> = 10) and females (<i>n</i> = 4) completed arm cycling bouts and isometric contractions of the elbow flexors. Indwelling fine-wire electrodes were inserted into the biceps brachii to record MUFRs during arm cycling with combinations of two power outputs (25 W and 50 W) and cadences (30 rpm and 60 rpm), and subsequently compared with intensity-matched isometric contractions. Motor unit recordings were analyzed during the flexion phase of arm cycling when biceps brachii EMG activity was high, and with the forearms in a neutral grip position. Results indicated that MUFRs were significantly higher during arm cycling compared with isometric contractions (<i>P</i> = 0.003), and MUFRs increased with greater cycling intensity (<i>P</i> < 0.001). Higher MUFRs demonstrated during arm cycling were likely influenced by greater descending drive and/or enhanced spinal motoneuron excitability, facilitated through central pattern generator (CPG)-mediated changes to intrinsic motoneuron properties. Thus, different neural control strategies are used during rhythmic locomotor output compared with isometric contractions in humans.<b>NEW & NOTEWORTHY</b> Motor unit firing rates (MUFRs) during an upper-limb locomotor task have yet to be recorded in humans, and behavior of the active motor units during dynamic central pattern generator (CPG)-mediated locomotor activity is currently unknown. The present study used indwelling fine-wire electrodes to record MUFRs during arm cycling and compared the firing rates to intensity-matched isometric contractions. Results demonstrated that MUFRs were significantly higher during arm cycling, indicating different neural control strategies between locomotor outputs and isometric contractions.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"162-170"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unpredictable movement-evoked pain alters cortical motor preparatory activity.","authors":"Emmanuel Ogalo, Hannah Ro, Oscar Ortiz, Lukas Linde, Michael J Berger, John Kramer","doi":"10.1152/jn.00237.2025","DOIUrl":"10.1152/jn.00237.2025","url":null,"abstract":"<p><p>Although there is substantial evidence that central motor system function is altered both during and after pain removal, the effect of pain on motor preparation remains poorly understood. The present study used electroencephalography (EEG) to examine whether the predictability of movement-evoked pain modulates cortical preparatory activity, and whether changes in cortical activity persist after the removal of pain. The movement-related cortical potential (MRCP), alpha frequency band (8-12 Hz) oscillatory activity, and the vertex laser-evoked potential (N2P2) were evaluated in 15 healthy adults (9 males, age = 30.3 ± 10.2 yr). Under unpredictable pain expectancy, peak MRCP amplitude (<i>P</i> = 0.044), premovement alpha activity (<i>P</i> = 0.002), and N2P2 amplitude (<i>P</i> < 0.001) all significantly increased. These preparatory changes did not persist once the pain was removed [MRCP: <i>P</i> = 1.0; alpha event-related spectral perturbation (ERSP): <i>P</i> = 1.0]. These findings suggest that unpredictable pain expectancy modulates motor preparation through top-down attentional mechanisms that serve to suppress distractor sensorimotor processing and enhance task-relevant neural activity to support optimal motor programming.<b>NEW & NOTEWORTHY</b> Our findings support a proactive suppression model of attention under unpredictability, in which cognitive resources are reallocated via enhanced alpha activity that aims to suppress forthcoming sensory processing to facilitate motor preparation of goal-directed movement. Furthermore, neural preparatory activity returns to baseline with the removal of pain suggesting preparatory activity is dynamic and current measures only provide a read-out of transient cortical states.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"264-273"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feelings on the tongue.","authors":"Jennifer Wheary, Tony Ro","doi":"10.1152/jn.00224.2025","DOIUrl":"10.1152/jn.00224.2025","url":null,"abstract":"","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"287-289"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complementary functional profiles of mismatch responses mediated by adaptation and deviance detection point to two distinct auditory short-term memory systems.","authors":"Tobias Teichert, Hank Jedema, Zhijun Zhen, Kate Gurnsey","doi":"10.1152/jn.00515.2024","DOIUrl":"10.1152/jn.00515.2024","url":null,"abstract":"<p><p>Mismatch negativity (MMN) is a macroscopic EEG deflection in response to potentially informative auditory events, e.g., rare or unexpected sounds. Mismatch negativity reflects two processes: <i>1</i>) adaptation, a reduction of responses to repeated sounds, and <i>2</i>) deviance detection, an enhancement of responses to sounds violating an expected pattern, likely mediated by predictive coding. Adaptation and deviance detection both reflect information about past sounds and are thus dependent on an auditory memory trace. Although the two processes have been distinguished theoretically, computationally, and anatomically, it is not known whether they use information from the same or different memory systems. To answer this question, macaque monkeys listened to a modified roving standard paradigm with a many-standard control condition designed to split mismatch responses into adaptation and deviance detection as a function of delay and frequency difference. Using computational modeling, we confirm that the requirements for isolating adaptation and deviance detection are met. We show that micro- and macroscopic mismatch responses were dominated by adaptation at short latencies but included a meaningful contribution of deviance detection at longer latencies. Most importantly, we show that mismatch responses mediated by adaptation have a short temporal scope and narrow frequency tuning consistent with its dependence on echoic memory. In contrast, mismatch responses mediated by deviance detection have a longer temporal scope but broader frequency tuning, thus pointing to a different memory system. These clearly distinct functional profiles shed light on the evolutionary need for two separate but complementary mechanisms for guiding attention to potentially informative auditory events.<b>NEW & NOTEWORTHY</b> Mismatch negativity has been viewed either as an echoic memory-based comparison process (deviance detection), or as the recruitment of nonadapted fresh afferents (adaptation). Here, we show that lifetime and frequency tuning of adaptation, but not deviance detection, matches that of echoic memory measured behaviorally. These findings provide compelling evidence that the mismatch negativity (MMN) is a mix of two functionally distinct processes whose properties reflect two distinct auditory memory systems.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"314-336"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}