Journal of Neuroscience最新文献

{"title":"GABAergic projections from the pretectum boost retinogeniculate signal transfer via disinhibition.","authors":"J B Whitley,S P Masterson,T Gordon,K L Whyland,P W Campbell,N Zhou,G Govindaiah,W Guido,M E Bickford","doi":"10.1523/jneurosci.2325-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2325-24.2025","url":null,"abstract":"The transfer of retinal signals from the dorsal lateral geniculate nucleus (dLGN) to the primary visual cortex (V1) is modulated by a variety of extraretinal inputs, including extrinsic connections formed by GABAergic neurons in the pretectum (PT) and visual sector of the thalamic reticular nucleus (vTRN), as well as the intrinsic connections of GABAergic dLGN interneurons. In the current study, we determined how GABAergic PT projections to the dLGN and vTRN can influence retinogeniculate transfer using a variety of viral tracing techniques, electron microscopy, in vitro physiological recordings, and optogenetics in male and female mice. We found that the PT provides over 75% of the GABAergic, and over 30% of the total synaptic input to the vTRN. Optogenetic activation of PT terminals reduced the firing frequency of vTRN neurons as well as the amplitudes of their postsynaptic responses to V1 input. In the dLGN, synaptic terminals originating from the PT targeted interneurons more frequently than thalamocortical (relay) cells, and optogenetic activation of PT input had a greater impact on interneuron firing frequency compared to relay cells. This cell type specific impact of PT input to the dLGN resulted in the disinhibition of relay cells and an increase in the amplitude of their postsynaptic responses to retinal input. Taken together, our results indicate that GABAergic PT projections to the visual thalamus serve to boost retinogeniculate transfer via two types of disinhibition, potentially enhancing the flow of visual information to V1 following gaze shifts.Significance Statement The transfer of visual information from the retina to the cortex must be coordinated with gaze shifts to explore the surrounding environment. Here we document pathways from the pretectum, a region responsive during gaze shifts, to the visual thalamus. We find that pretectum neurons that use the inhibitory neurotransmitter gamma amino butyric acid (GABA) selectively innervate GABAergic neurons in the thalamic reticular nucleus and dorsal lateral geniculate nucleus, which serves to boost the transfer of visual information from the thalamus to the cortex. The identification of these brain circuits may have important implications for disorders of gaze shifts and/or sensory modulation.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"56 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836506","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":"Functional heterogeneity within the primate ventral striatum for motivational regulation.","authors":"Haruhiko Iwaoki,Yukiko Hori,Yuki Hori,Koki Mimura,Kei Oyama,Yuji Nagai,Toshiyuki Hirabayashi,Ken-Ichi Inoue,Masahiko Takada,Makoto Higuchi,Takafumi Minamimoto","doi":"10.1523/jneurosci.2430-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2430-24.2025","url":null,"abstract":"The ventral striatum (VS) is a key brain region for reward processing and motivation, and its dysfunctions have been implicated in psychiatric disorders such as apathy and obsessive-compulsive disorder. Although functional heterogeneity within the VS has been well established in rodents, its relevance and mechanisms in primates remain unclear. To address this issue, we performed bilateral pharmacological inactivation of the VS in two male macaque monkeys using muscimol, a GABAA receptor agonist. Precise targeting was achieved through computed tomography and magnetic resonance imaging. Behavioral effects were evaluated using two methods: a goal-directed task with variable rewards and analysis of spontaneous behavior. Our results demonstrated that anterior (a)VS inactivation induced a hypoactivity state that we termed \"resting,\" whereas posterior (p)VS inactivation elicited compulsive-like \"checking\" behaviors. Notably, neither the aVS nor the pVS inactivation affected reward value or drive processing, thus differentiating aVS and pVS from those involved in incentive motivation, such as the rostromedial caudate and ventral pallidum. Retrograde tracing demonstrated distinct anatomical projection patterns for the aVS and pVS, supporting their functional segregation. Together, the present results suggest the functional heterogeneity of the primate VS along its anterior-posterior axis, with the aVS and pVS participating in distinct motivational control circuits. Our findings may have important implications for understanding the neural mechanisms of psychiatric disorders and for the development of new therapeutic approaches.Significance Statement The ventral striatum (VS) is a core brain region that is involved in motivation and reward-based behaviors. Its dysfunction is implicated in psychiatric disorders such as apathy and obsessive-compulsive disorder. In macaque monkeys, we used imaging-guided pharmacological manipulations to reveal that the anterior and posterior VS subregions have distinct roles in motivation, independent of the incentive or reward drive. Specifically, anterior VS inactivation induced a hypoactive state, whereas posterior VS inactivation elicited compulsive-like behaviors. These findings reveal distinct motivational mechanisms within the primate VS, thus offering valuable insights into the neural basis of psychiatric disorders and identifying promising therapeutic targets.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"5 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836507","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":"Mitochondrial glutamine metabolism drives epileptogenesis in primary hippocampal neurons.","authors":"Helmut Kubista,Francesco Gentile,Klaus Schicker,Thomas Köcher,Stefan Boehm,Matej Hotka","doi":"10.1523/jneurosci.0110-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0110-25.2025","url":null,"abstract":"All available anti-seizure medications aim at symptomatic control of epilepsy, but there is no strategy to stop the development of the disease. The main reason is the lack of understanding of the epileptogenic mechanisms. Closing this knowledge gap is an essential prerequisite for developing disease-modifying therapies that can prevent the onset of epilepsy. Using primary co-cultures of hippocampal neurons and glial cells derived from rat pups of either sex, we show that epileptiform paroxysmal depolarization shifts (PDS) induce neuronal glucose hypometabolism which is compensated for by increased glutaminolysis. Glutaminolysis not only provides sufficient ATP to support electrical activity, but also leads to decreased vesicular glutamate release, thereby promoting neuronal hypersynchrony. Moreover, prolonged promotion of PDS increased neuronal arborization and synaptic density, which in combination with spontaneous recovery of neuronal glucose metabolism led to seizure-like discharge activity. Since inhibition of glutaminolysis did not prevent the PDS-induced morphogenesis, but eliminated seizure-like activity, we propose that glutaminolysis is a causative process linking neuronal metabolism with electrical activity thereby driving epileptogenesis.Significance statement The available pharmacotherapy for epilepsy provides symptomatic control of seizures by interfering with ictogenesis. However, understanding the preceding epileptogenic processes would offer an opportunity to intervene in the development of the disease. The electrical activity and glucose metabolism of the brain regions corresponding to the epileptic foci are disturbed long before the first seizures occur. The significance of the altered neuronal activity and metabolism is not well understood. We present evidence that abnormal neuronal electrical activity called paroxysmal depolarization shifts increase neuronal arborization and lead to metabolic shifts making neurons transiently rely on glutamine. We show that the interplay of these processes induces glucose hypometabolism, hyper-synchronization, and ultimately leads to seizure-like discharge activity, thus replicating several key features of epilepsy.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"66 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836508","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":"Impact of rod-dominant mesopic conditions on spatial summation and surround suppression in early visual cortex.","authors":"Michaela Klimova,MiYoung Kwon","doi":"10.1523/jneurosci.1649-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1649-24.2025","url":null,"abstract":"Mesopic (dim light) conditions are prevalent in everyday environments, yet most human vision research is conducted under idealized, photopic (bright) conditions. Electrophysiological studies suggest that under mesopic conditions, retinal ganglion cell receptive fields, which encode contrast, expand their center width while diminishing surround inhibition. These retinal modifications enhance light capture by increasing the summation area but they limit spatial resolution. However, the impact of mesopic conditions on human cortical spatial integration mechanisms remains unclear. To address this, we investigate how mesopic conditions affect early visuocortical processing, specifically spatial summation and surround suppression. Across two experiments, we acquired fMRI BOLD responses from 11 normally-sighted participants of both sexes under photopic and mesopic conditions in visual areas V1 - V3. The first experiment estimated population receptive field (pRF) properties while the second experiment assessed cortical surround suppression. Photopic and mesopic psychophysical surround suppression, Contrast Sensitivity Function (CSF), and visual acuity were also measured. At the cortical level, mesopic conditions were associated with smaller pRF sizes, while surround suppression remained robust. At the perceptual level, mesopic conditions led to reduced acuity, lower CSF, and weaker suppression, diverging from the observed cortical effects. Importantly, individual differences linked these findings: participants who exhibited greater mesopic reductions in visual acuity also showed larger decreases in early visuocortical surround suppression, underscoring its role in contrast coding and spatial resolution. Altogether, our fMRI findings contrast with retinal electrophysiology and suggest that early visual cortex may employ distinct, perhaps compensatory, mechanisms in response to reduced retinal input under mesopic conditions.Significance Statement Despite the prevalence of mesopic (dim light) environments, their impact on human visuocortical processing remains understudied. Electrophysiological studies suggest that mesopic conditions lead to larger receptive fields and reduced surround inhibition in retinal ganglion cells, enhancing light summation at the cost of spatial resolution. Using fMRI and psychophysical measurements, we investigate how mesopic conditions impact spatial summation and surround suppression across early visual cortex. We find that under mesopic conditions, population receptive fields become smaller, and cortical surround suppression remains robust. However, individual differences revealed a correlation between mesopic visual acuity impairment and changes in V1 surround suppression. These findings contrast with retinal electrophysiological findings, pointing to potential cortical refinement mechanisms that help preserve visual function under degraded viewing conditions.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"42 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836512","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":"Joint Heritability of Sleep EEG Spindle Activity and Thalamic Volume in Early Adolescence.","authors":"Andjela Markovic,Duco Veen,Christoph Hamann,Kristina Adorjan,Michael Kaess,Ruth Tuura O'Gorman,Leila Tarokh","doi":"10.1523/jneurosci.1138-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1138-24.2025","url":null,"abstract":"Sleep spindles, transient bursts of rhythmic activity during non-rapid eye movement (NREM) sleep, are generated by the thalamocortical network through an intricate interplay between the thalamus and the cortex. Emerging research has shed light on the role of sleep spindles in cognitive function, memory consolidation, and overall brain health. Using a behavioral genetics approach in female and male adolescent humans, this study examined the degree to which sleep spindles (measured via high-density sleep EEG) and thalamic volume (measured via MRI) are driven by common genetic and environmental factors. Here we show a strong correlation between thalamic volume and sleep spindle amplitude and density. Bayesian structural equation modelling estimated that over posterior regions genetic factors accounted for approximately half of the covariance between sleep spindle activity and thalamic volume. Our findings demonstrate that genetic factors play a role in shaping the structural and functional integrity of the thalamocortical network, with implications for understanding how these processes contribute to neurodevelopmental outcomes.Significance statement Sleep spindles, oscillatory activity generated in the thalamus, are crucial for cognitive functions and brain health. This study investigated the joint genetic and environmental influences on sleep spindles and thalamic volume in adolescents. Our findings suggest a significant overlap in genetic factors influencing thalamic volume and spindle amplitude over posterior brain regions. Given that sleep spindle activity is altered in several brain disorders involving the thalamocortical system, this work not only enhances our understanding of the biological phenomena underlying the neuroanatomical substrates of the sleep EEG but also offers crucial insights for developing targeted interventions in neurodevelopmental disorders.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"39 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824783","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 administration of ketamine is associated with dose-dependent stabilization of cortical dynamics in humans.","authors":"Diego G Dávila,Andrew McKinstry-Wu,Max B Kelz,Alex Proekt","doi":"10.1523/jneurosci.1545-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1545-24.2025","url":null,"abstract":"During wakefulness, external stimuli elicit conscious experiences. In contrast, dreams and drug-induced dissociated states, are characterized by vivid internally generated conscious experiences and reduced ability to perceive external stimuli. Understanding the physiological distinctions between normal wakefulness and dissociated states may therefore disambiguate signatures of responsiveness to external stimuli from those that underlie conscious experience. The hypothesis that conscious experiences are associated with brain criticality has received considerable theoretical and experimental support. Consistent with this hypothesis, statistical signatures of criticality are similar in normal wakefulness and dissociative states but are abolished in dreamless sleep and under anesthesia. Thus, while statistical measures of criticality are associated with the ability to have conscious experience, they do not readily distinguish between perception of the external world from internally generated percepts. Here, we investigate distinct, dynamical, signatures of criticality during escalating ketamine doses in high-density EEG in human male volunteers. We show that during normal wakefulness, EEG is found at a critical point between damped and exploding oscillations. With increasing doses of ketamine, as dissociative symptoms intensify, activity is progressively stabilized - most prominently at higher frequencies. We also show that stabilization is a more reliable marker of the effects of ketamine than conventional measures such as power spectra. These findings suggest that stabilization of cortical dynamics correlates with decreased ability to respond to and perceive external stimuli rather than the ability to have conscious experiences per se. Altogether, these results suggest that combining statistical and dynamical criticality measures may distinguish wakefulness, dissociation, and unconsciousness.Significance Statement During wakefulness, external stimuli elicit sensory perceptions while during unconsciousness, perception is absent. Dissociated states of consciousness, including those induced by ketamine, feature internally generated experiences and, concomitantly, reduced responsiveness to stimuli. Both normal wakefulness and dissociated states have been linked to statistical criticality, a regime in which the brain operates at the transition between order and disorder. Here, we study a distinct notion of criticality - transition between stable and unstable oscillations and show that ketamine induces dose-dependent stabilization of normally critical brain dynamics. Thus, departure from dynamical criticality is associated with states of reduced responsiveness rather than unconsciousness. Combining statistical and dynamical criticality measures may better distinguish connected and dissociated states of consciousness.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"43 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819222","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":"Optogenetic stimulation of novel TPH2-Cre rats advances insight into serotonin's role in locomotion, reinforcement, and compulsivity.","authors":"Rhiannon Robke,Francesca Sansi,Tara Arbab,Adria Tunez Aquilue,Miranda Moore,Dusan Bartsch,Kai Schönig,Ingo Willuhn","doi":"10.1523/jneurosci.1424-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1424-24.2025","url":null,"abstract":"Serotonin critically modulates the activity of many brain networks, including circuits that control motivation and responses to rewarding and aversive stimuli. Furthermore, the serotonin system is targeted by the first line of pharmacological treatment for several psychiatric disorders, such as obsessive-compulsive disorder. However, understanding the behavioral function of serotonin is hampered by methodological limitations: the (brainstem) location of serotonergic neuron cell bodies is difficult to access, their innervation of the brain is diffuse, and they release serotonin in relatively low concentrations. Here, we advance this effort by developing a novel Tph2-Cre rat line, which we utilized to study serotonin in the context of motor, compulsive, and reinforced behaviors using optogenetics in both male and female rats. Specificity and sensitivity of Cre-recombinase expression and Cre-dependent processes was validated immunohistochemically, and optogenetic induction of in-vivo serotonin release was validated with fast-scan cyclic voltammetry. Optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus did not initiate locomotion or alter aversion-induced locomotion, nor did it elicit (real-time) place preference, and had no measurable effect on compulsive behavior in the schedule-induced polydipsia task. In contrast, this optogenetic stimulation moderately sustained ongoing spontaneous locomotion and robustly reinforced operant lever-pressing for self-stimulation of serotonin neurons, which was exacerbated by food restriction. Together, this work both introduces a novel rat Cre-line to study serotonin, and advances our understanding of serotonin's behavioral functions. Complementing previous findings, we find that brain-wide serotonin release has an overall relatively mild effect on behavior, which manifested only in the absence of natural reinforcers and was modulated by physiological state.Significance Statement Although serotonin is produced by only a very small number of neurons, it modulates the activity of almost all brain networks and is implicated in numerous behavioral functions and many psychiatric disorders. However, our comprehension of serotonin function and dysfunction is hampered by methodological limitations, which can be improved by our novel Tph2-Cre rat line. We investigated general behavioral processes to principally understand serotonergic involvement in the many functions it has been implicated in. Complementing and furthering previous findings and consistent with its low concentrations found ubiquitously throughout the brain, we find that brain-wide serotonin release has mild effects on behavior, which are modulated by hunger and manifest only in the absence of food reward in the experimental environment.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"33 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819230","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":"Neuronal synchronization and bidirectional activity spread explain efficient swimming in a whole-body model of hydrozoan jellyfish.","authors":"Fabian Pallasdies,Philipp Norton,Jan-Hendrik Schleimer,Susanne Schreiber","doi":"10.1523/jneurosci.1370-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1370-24.2025","url":null,"abstract":"Aquatic animals need tightly choreographed movements to efficiently navigate through open waters. Radially symmetric animals, like jellyfish, face the additional challenge of having to respond to regionalized sensory stimuli at the margin of their bell with an orchestrated motor response that initiates predation or escape. The nerve net of hydrozoan jellyfish comprises a condensed ring of electrically coupled neurons, that process sensory input and control the motor output. Here we aim to understand the coupling of neural activity and motor response by developing a biophysical computational model of the swimming-motor-net of a hydrozoan jellyfish and let it control a swimming jellyfish in a fluid simulation. We find that the neuron activity can synchronize while the signal travels around the ring, eventually triggering a bidirectional wave of activation in the muscles. This mechanism explains seemingly contradicting electrophysiological experiments and minimizes muscle contraction time. Hydrodynamical simulations demonstrate that this setup enables symmetric movement even if neural input is highly asymmetric. We hypothesize that the development of this ring structure supports the jet propulsion by which hydrozoan jellyfish swim. These findings show the importance of considering whole body anatomy and movement when investigating neural design.Significance Statement Hydrozoan jellyfish use simple nerve nets for muscle activation to swim forward by ejecting water with their bell-shaped body. How a directed swimming stroke is created from spatially-coordinated activation of their nerve and muscle nets is currently not understood. We demonstrate that these jellyfish use an unexpected strategy involving synchronization of electrical pulses in their nerve net, triggering a parallel spread of activity in different sections of the muscle ring and resulting in a significant reduction of the muscle contraction time. Fluid-dynamical simulations of the whole animal in its aquatic environment show that this clever activation mechanism fosters efficient swimming. The study provides a rare example of a complete mechanistic explanation of animal behavior from cellular biophysics to whole-body movement.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"39 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819226","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":"Dorsal-caudal and ventral hippocampus target different cell populations in the medial frontal cortex in rodents.","authors":"Paola Alemán-Andrade,Menno P Witter,Ken-Ichiro Tsutsui,Shinya Ohara","doi":"10.1523/jneurosci.0217-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0217-25.2025","url":null,"abstract":"Direct projections from the ventral hippocampus (vHPC) to the medial frontal cortex (MFC) play crucial roles in memory and emotional regulation. Using anterograde transsynaptic tracing and ex vivo electrophysiology in male mice, we document a previously unexplored pathway that parallels the established vHPC-MFC connectivity. This pathway connects the dorsal-caudal hippocampus (dcHPC) to specific subregions of the ventral MFC, in particular the dorsal peduncular cortex. Notably, this pathway exerts a strong inhibitory influence on ventral MFC by targeting a substantial proportion of inhibitory neurons. Retrograde transsynaptic tracing in male rats indicated that ventral MFC subregions project disynaptically back to vHPC. These results, altogether, suggest the existence of a remarkable functional circuit connecting distinct functional areas: the cognition-related dcHPC with the emotion-related ventral MFC and vHPC. These findings further provide valuable insights in the cognitive and emotional abnormalities associated with the HPC-MFC connectivity in neurological and psychiatric disorders.Significance of statement We re-examined the organization of the circuits connecting the hippocampus (HPC) to the medial frontal cortex (MFC) in rodents. We found that dorsal-caudal HPC innervates robustly neurons in ventral subregions of MFC, particularly the dorsal peduncular cortex (DP), including a significant population of inhibitory neurons. Our results show that DP, a subregion critical for emotional and autonomic control, can be modulated by the direct projection from the more cognition-related dorsal-caudal HPC.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"3 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819225","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":"Multimodal Correspondence Between Optogenetic fMRI, Electrophysiology, and Anatomical Maps of the Secondary Somatosensory Cortex in Nonhuman Primates.","authors":"Pai-Feng Yang,Jamie Reed,Zhangyan Yang,Feng Wang,Ning Zheng,John C Gore,Li Min Chen","doi":"10.1523/jneurosci.2375-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.2375-24.2025","url":null,"abstract":"Optogenetic neuromodulation combined with fMRI (opto-fMRI) enables noninvasive monitoring of brain-wide activity and probs causal connections. In this study, we focused on the secondary somatosensory cortex (S2), a hub for integrating tactile and nociceptive information. By selectively stimulating excitatory neurons in the S2 cortex of monkeys using optogenetics, we observed widespread opto-fMRI activity in regions beyond the somatosensory system, as well as a strong spatial correspondence between opto-fMRI activity map and anatomical connections of the S2 cortex. Locally, optogenetically evoked fMRI BOLD signals from putative excitatory neurons exhibited standard hemodynamic response function. At low laser power, graded opto-fMRI signal changes are closely correlated with increases in LFP signals, but not with spiking activity. This indicates that LFP changes in excitatory neurons more accurately reflect the opto-fMRI signals than spikes. In summary, our optogenetic fMRI and anatomical findings provide causal functional and anatomical evidence supporting the role of the S2 cortex as a critical hub connecting sensory regions to higher-order cortical and subcortical regions involved in cognition and emotion. The electrophysiological basis of the opto-fMRI signals uncovered in this study offers novel insights into interpreting opto-fMRI results. Non-human primates are an invaluable intermediate model for translating optogenetic preclinical findings to humans.Significance statement The neocortex consists of excitatory and inhibitory neurons, each playing distinct roles in cognition and contributing to brain disorders. This study marks the first to use optogenetics to selectively stimulate excitatory neurons of the primate somatosensory S2 cortex, establishing a spatial correspondence between brain-wide opto-fMRI activity and anatomical tracer-based connections in the S2 hand region. The differential relationships between laser power and changes in BOLD, local field potentials, and spiking activity suggest that LFP signals better reflect opto-fMRI signals at the excitatory neuron population level. This work has translational potential for developing targeted neuromodulation therapies for neurological and psychiatric disorders. Success in NHPs, along with advances in noninvasive AAV delivery, paves the way for future clinical applications.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"25 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819228","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}