Patterns Of Neuronal Activity Research Articles

Memory traces of duration and location in the right intraparietal sulcus

Time and space form an integral part of every human experience, and for the neuronal representation of these perceptual dimensions, previous studies point to the involvement of the right-hemispheric intraparietal sulcus and structures in the medial temporal lobe. Here we used multi-voxel pattern analysis (MVPA) to investigate long-term memory traces for temporal and spatial stimulus features in those areas. Participants were trained on four images associated with short versus long durations and with left versus right locations. Our results demonstrate stable representations of both temporal and spatial information in the right posterior intraparietal sulcus. Building upon previous findings of stable neuronal codes for directly perceived durations and locations, these results show that the reactivation of long-term memory traces for temporal and spatial features can be decoded from neuronal activation patterns in the right parietal cortex.

Patterns of neuronal activation following ethanol-induced social facilitation and social inhibition in adolescent cFos-LacZ male and female rats

Alcohol-associated social facilitation together with attenuated sensitivity to adverse alcohol effects play a substantial role in adolescent alcohol use and misuse, with adolescent females being more susceptible to adverse consequences of binge drinking than adolescent males. Adolescent rodents also demonstrate individual and sex differences in sensitivity to ethanol-induced social facilitation and social inhibition, therefore the current study was designed to identify neuronal activation patterns associated with ethanol-induced social facilitation and ethanol-induced social inhibition in male and female adolescent cFos-LacZ rats. Experimental subjects were given social interaction tests on postnatal day (P) 34, 36, and 38 after an acute challenge with 0, 0.5 and 0.75 g/kg ethanol, respectively, and β-galactosidase (β-gal) expression was assessed in brain tissue of subjects socially facilitated and socially inhibited by 0.75 g/kg ethanol. In females, positive correlations were evident between overall social activity and neuronal activation of seven out of 13 ROIs, including the prefrontal cortex and nucleus accumbens, with negative correlations evident in males. Assessments of neuronal activation patterns revealed drastic sex differences between ethanol responding phenotypes. In socially inhibited males, strong correlations were evident among almost all ROIs (90 %), with markedly fewer correlations among ROIs (38 %) seen in socially facilitated males. In contrast, interconnectivity in females inhibited by ethanol was only 10 % compared to nearly 60 % in facilitated subjects. However, hub analyses revealed convergence of brain regions in males and females, with the nucleus accumbens being a hub region in socially inhibited subjects. Taken together, these findings demonstrate individual and sex-related differences in responsiveness to acute ethanol in adolescent rats, with sex differences more evident in socially inhibited by ethanol adolescents than their socially facilitated counterparts.

Promiscuous involvement of metabotropic glutamate receptors in the storage of N-methyl-d-aspartate receptor-dependent short-term potentiation.

Short- and long-term forms of N-methyl-d-aspartate receptor (NMDAR)-dependent potentiation (most commonly termed short-term potentiation (STP) and long-term potentiation (LTP)) are co-induced in hippocampal slices by theta-burst stimulation, which mimics naturally occurring patterns of neuronal activity. While NMDAR-dependent LTP (NMDAR-LTP) is said to be the cellular correlate of long-term memory storage, NMDAR-dependent STP (NMDAR-STP) is thought to underlie the encoding of shorter-lasting memories. The mechanisms of NMDAR-LTP have been researched much more extensively than those of NMDAR-STP, which is characterized by its extreme stimulation dependence. Thus, in the absence of low-frequency test stimulation, which is used to test the magnitude of potentiation, NMDAR-STP does not decline until the stimulation is resumed. NMDAR-STP represents, therefore, an inverse variant of Hebbian synaptic plasticity, illustrating that inactive synapses can retain their strength unchanged until they become active again. The mechanisms, by which NMDAR-STP is stored in synapses without a decrement, are unknown and we report here that activation of metabotropic glutamate receptors may be critical in maintaining the potentiated state of synaptic transmission. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Nonfrontal Control of Working Memory.

Items held in visual working memory can be quickly updated, replaced, removed, and even manipulated in accordance with current behavioral goals. Here, we use multivariate pattern analyses to identify the patterns of neuronal activity that realize the executive control processes supervising these flexible stores. We find that portions of the middle temporal gyrus and the intraparietal sulcus represent what item is cued for continued memorization independently of representations of the item itself. Importantly, this selection-specific activity could not be explained by sensory representations of the cue and is only present when control is exerted. Our results suggest that the selection of memorized items might be controlled in a distributed and decentralized fashion. This evidence provides an alternative perspective to the notion of "domain general" central executive control over memory function.

Reactivation strength during cued recall is modulated by graph distance within cognitive maps.

Declarative memory retrieval is thought to involve reinstatement of neuronal activity patterns elicited and encoded during a prior learning episode. Furthermore, it is suggested that two mechanisms operate during reinstatement, dependent on task demands: individual memory items can be reactivated simultaneously as a clustered occurrence or, alternatively, replayed sequentially as temporally separate instances. In the current study, participants learned associations between images that were embedded in a directed graph network and retained this information over a brief 8 min consolidation period. During a subsequent cued recall session, participants retrieved the learned information while undergoing magnetoencephalographic recording. Using a trained stimulus decoder, we found evidence for clustered reactivation of learned material. Reactivation strength of individual items during clustered reactivation decreased as a function of increasing graph distance, an ordering present solely for successful retrieval but not for retrieval failure. In line with previous research, we found evidence that sequential replay was dependent on retrieval performance and was most evident in low performers. The results provide evidence for distinct performance-dependent retrieval mechanisms, with graded clustered reactivation emerging as a plausible mechanism to search within abstract cognitive maps.

Reactivation strength during cued recall is modulated by graph distance within cognitive maps

Declarative memory retrieval is thought to involve reinstatement of neuronal activity patterns elicited and encoded during a prior learning episode. Furthermore, it is suggested that two mechanisms operate during reinstatement, dependent on task demands: individual memory items can be reactivated simultaneously as a clustered occurrence or, alternatively, replayed sequentially as temporally separate instances. In the current study, participants learned associations between images that were embedded in a directed graph network and retained this information over a brief 8 min consolidation period. During a subsequent cued recall session, participants retrieved the learned information while undergoing magnetoencephalographic recording. Using a trained stimulus decoder, we found evidence for clustered reactivation of learned material. Reactivation strength of individual items during clustered reactivation decreased as a function of increasing graph distance, an ordering present solely for successful retrieval but not for retrieval failure. In line with previous research, we found evidence that sequential replay was dependent on retrieval performance and was most evident in low performers. The results provide evidence for distinct performance-dependent retrieval mechanisms, with graded clustered reactivation emerging as a plausible mechanism to search within abstract cognitive maps.

Hyperexcitation of ovBNST CRF neurons during stress contributes to female-biased expression of anxiety-like avoidance behaviors.

Corticotropin releasing factor (CRF) network in the oval nucleus of bed nuclei of the stria terminalis (ovBNST) is generally indicated in stress, but its role in female-biased susceptibility to anxiety is unknown. Here, we established a female-biased stress paradigm. We found that the CRF release in ovBNST during stress showed female-biased pattern, and ovBNST CRF neurons were more prone to be hyperexcited in female mice during stress in both in vitro and in vivo studies. Moreover, optogenetic modulation to exchange the activation pattern of ovBNST CRF neurons during stress between female and male mice could reverse their susceptibility to anxiety. Last, CRF receptor type 1 (CRFR1) mediated the CRF-induced excitation of ovBNST CRF neurons and showed female-biased expression. Specific knockdown of the CRFR1 level in ovBNST CRF neurons in female or overexpression that in male could reverse their susceptibility to anxiety. Therefore, we identify that CRFR1-mediated hyperexcitation of ovBNST CRF neurons in female mice encode the female-biased susceptibility to anxiety.

High-Fat Diet Alters Neuronal Activity in Cardiometabolic-Regulatory Brain Regions in a Sex-Specific Manner

Obesity is a major public health problem that is associated with dysregulation of central nervous system circuits controlling cardiovascular and metabolic functions. High-fat diet (HFD)-induced obesity in animal models is known to widely influence neuronal function in metabolic-regulatory brain regions; however, the impact of HFD, and its interactions with sex, on neuronal activity in cardiovascular-regulatory brain regions is not fully understood. Thus, the objective of this study was to investigate differences in c-fos expression, a marker of neuronal activity, in key brain regions involved in cardiometabolic regulation in HFD-induced obese mice. We hypothesized that HFD would alter the pattern of neuronal activity in hypothalamic and brainstem regions in a sex-specific manner. To test this, male and female C57Bl/6J mice (n=6/group) were placed on a 60% HFD or matched control diet for 14 weeks. At the end of the diet period, brains were collected to assess for c-fos immunoreactivity in the paraventricular nucleus (PVN) and arcuate nucleus (ARC) of the hypothalamus, as well as in the nucleus of the solitary tract (NTS) and rostral ventrolateral medulla (RVLM) of the brainstem. Brain slices were imaged using a Keyence Fluorescent Microscope and c-fos positive cells were counted using QuPath software in a blinded manner. There was a significant effect due to a sex-by-diet interaction in all brain regions, with female mice having a lower number of c-fos positive neurons compared to males overall, and even more so under HFD conditions (PVN: 132±21 male control vs. 183±28 male HFD vs. 136±21 female control vs. 89±10 female HFD, Pdiet=0.916, Psex=0.041, Pint=0.028 two-way ANOVA; ARC: 92±23 male control vs. 108±16 male HFD vs. 90±7 female control vs. 41±6 female HFD, Pdiet=0.272, Psex=0.024, Pint=0.039; NTS: 72±20 male control vs. 114±115 male HFD vs. 68±10 female control vs. 31±6 female HFD, Pdiet=0.885, Psex=0.004, Pint=0.009; RVLM: 59±12 male control vs. 105±11 male HFD vs. 59±12 female control vs. 28±5 female HFD, Pdiet=0.464, Psex=0.002, Pint=0.002). Overall, these data suggest there are sex-specific differences in neuronal activity within key brain regions integral to cardiometabolic control, which may be influenced by HFD in females. Future studies will need to assess the importance of these changes in neural activity to functional outcomes under normal conditions, and in the context of obesity. Funding: NIH R01 HL156986. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lumbar epidural electrical stimulation enhances respiration in mice

Spinal cord epidural electrical stimulation (EES) has emerged as a novel approach to modulate and interrogate the neural circuit(s) underlying sensorimotor functions in the past few decades. Recent studies have revealed that cervical EES can regulate respiration in both human subjects and animal models. Furthermore, coupled cervical and lumbar stimulations significantly increased the rhythmic motor outputs in both the cervical and lumbar spinal cord. We hypothesize that the lumbar and cervical coupling is underpinned by cervico-lumbar synaptic connections, and thus, EES at level of the lumbar spinal cord alone may also facilitate respiration via the cervico-lumbar circuit. In this study, we applied EES to the dorsal surface of the lumbar spinal cord between levels 1 and 6 (L1-6) in anesthetized mice. We found that rostral lumbar (L1-2) EES at a stimulation intensity of 0.5 mA elicited significantly higher respiratory frequency, tidal volume, and minute ventilation responses compared to the other lumbar levels (L3-4 and L5-6) tested at intensities ranging from 0.1-1.0 mA. The increased respiratory activity elicited by lumbar stimulation persisted even after the stimulation ceased. Using the optimal stimulation parameters that we identified, we further investigated the underlying mechanism of the lumbar EES-induced respiratory response by examining the neuronal activation patterns. Using immunostaining, we detected c-fos signals, a marker of neuronal activity, in the cervical spinal cord and brainstem after EES at L1-2 using 0.5 mA at 30Hz. This indicates that focal lumbar stimulation elicits remote neuronal activation in cervical spinal cord and brainstem, regions that contain respiration-related neural circuits. These findings suggest that lumbar EES may facilitate respiration by recruiting paraspinal respiratory circuits and potentially supra-spinal respiratory central pattern generator(s). This study provides insights into the development of novel approaches to restore normal respiratory patterns for patients with respiratory disorders, particularly spinal cord injuries. This work was supported by The Louis and Harold Price Foundation, H & H Evergreen Foundation, Jonathan and Susan Dolgen Foundation, the National Institute of Drug Abuse (R01DA047637), and the National Institute of Neurological Disorders and Stroke (UH3NS119772) in the National Institutes of Health. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Adolescent nicotine exposure induces long-term, sex-specific disturbances in mood and anxiety-related behavioral, neuronal and molecular phenotypes in the mesocorticolimbic system.

The majority of lifetime smokers begin using nicotine during adolescence, a critical period of brain development wherein neural circuits critical for mood, affect and cognition are vulnerable to drug-related insults. Specifically, brain regions such as the medial prefrontal cortex (mPFC), the ventral tegmental area (VTA), nucleus accumbens (NAc) and hippocampus, are implicated in both nicotine dependence and pathological phenotypes linked to mood and anxiety disorders. Clinical studies report that females experience higher rates of mood/anxiety disorders and are more resistant to smoking cessation therapies, suggesting potential sex-specific responses to nicotine exposure and later-life neuropsychiatric risk. However, the potential neural and molecular mechanisms underlying such sex differences are not clear. In the present study, we compared the impacts of adolescent nicotine exposure in male vs. female rat cohorts. We performed a combination of behavioral, electrophysiological and targeted protein expression analyses along with matrix assisted laser deionization imaging (MALDI) immediately post-adolescent exposure and later in early adulthood. We report that adolescent nicotine exposure induced long-lasting anxiety/depressive-like behaviors, disrupted neuronal activity patterns in the mPFC-VTA network and molecular alterations in various neural regions linked to affect, anxiety and cognition. Remarkably, these phenotypes were only observed in males and/or were expressed in the opposite direction in females. These findings identify a series of novel, sex-selective biomarkers for adolescent nicotine-induced neuropsychiatric risk, persisting into adulthood.

Characterization of Ultrasonic Vocalization-Modulated Neurons in Rat Motor Cortex Based on Their Activity Modulation and Axonal Projection to the Periaqueductal Gray.

Vocalization, a means of social communication, is prevalent among many species, including humans. Both rats and mice use ultrasonic vocalizations (USVs) in various social contexts and affective states. The motor cortex is hypothesized to be involved in precisely controlling USVs through connections with critical regions of the brain for vocalization, such as the periaqueductal gray matter (PAG). However, it is unclear how neurons in the motor cortex are modulated during USVs. Moreover, the relationship between USV modulation of neurons and anatomical connections from the motor cortex to PAG is also not clearly understood. In this study, we first characterized the activity patterns of neurons in the primary and secondary motor cortices during emission of USVs in rats using large-scale electrophysiological recordings. We also examined the axonal projection of the motor cortex to PAG using retrograde labeling and identified two clusters of PAG-projecting neurons in the anterior and posterior parts of the motor cortex. The neural activity patterns around the emission of USVs differed between the anterior and posterior regions, which were divided based on the distribution of PAG-projecting neurons in the motor cortex. Furthermore, using optogenetic tagging, we recorded the USV modulation of PAG-projecting neurons in the posterior part of the motor cortex and found that they showed predominantly sustained excitatory responses during USVs. These results contribute to our understanding of the involvement of the motor cortex in the generation of USV at the neuronal and circuit levels.

Correlational patterns of neuronal activation and epigenetic marks in the basolateral amygdala and piriform cortex following olfactory threat conditioning and extinction in rats.

Cumulative evidence suggests that sensory cortices interact with the basolateral amygdala (BLA) defense circuitry to mediate threat conditioning, memory retrieval, and extinction learning. The olfactory piriform cortex (PC) has been posited as a critical site for olfactory associative memory. Recently, we have shown that N-methyl-D-aspartate receptor (NMDAR)-dependent plasticity in the PC critically underpins olfactory threat extinction. Aging-associated impairment of olfactory threat extinction is related to the hypofunction of NMDARs in the PC. In this study, we investigated activation of neuronal cFos and epigenetic marks in the BLA and PC using immunohistochemistry, following olfactory threat conditioning and extinction learning in rats. We found highly correlated cFos activation between the posterior PC (pPC) and BLA. cFos was correlated with the degree of behavioral freezing in the pPC in both adult and aged rats, and in the BLA only in adult rats. Markers of DNA methylation 5 mC and histone acetylation H3K9/K14ac, H3K27ac, and H4ac exhibited distinct training-, region-, and age-dependent patterns of activation. Strong correlations of epigenetic marks between the BLA and pPC in adult rats were found to be a general feature. Conversely, aged rats only exhibited correlations of H3 acetylations between the two structures. Histone acetylation varied as a function of aging, revealed by a reduction of H3K9/K14ac and an increase of H4ac in aged brains at basal condition and following threat conditioning. These findings underscore the coordinated role of PC and BLA in olfactory associative memory storage and extinction, with implications for understanding aging related cognitive decline.

Defined co-cultures of glutamatergic and GABAergic neurons with a mutation in DISC1 reveal aberrant phenotypes in GABAergic neurons

BackgroundMutations in the gene DISC1 are associated with increased risk for schizophrenia, bipolar disorder and major depression. The study of mutated DISC1 represents a well-known and comprehensively characterized approach to understand neuropsychiatric disease mechanisms. However, previous studies have mainly used animal models or rather heterogeneous populations of iPSC-derived neurons, generated by undirected differentiation, to study the effects of DISC1 disruption. Since major hypotheses to explain neurodevelopmental, psychiatric disorders rely on altered neuronal connectivity observed in patients, an ideal iPSC-based model requires accurate representation of the structure and complexity of neuronal circuitries. In this study, we made use of an isogenic cell line with a mutation in DISC1 to study neuronal synaptic phenotypes in a culture system comprising a defined ratio of NGN2 and ASCL1/DLX2 (AD2)-transduced neurons, enriched for glutamatergic and GABAergic neurons, respectively, to mimic properties of the cortical microcircuitry.ResultsIn heterozygous DISC1 mutant neurons, we replicated the expected phenotypes including altered neural progenitor proliferation as well as neurite outgrowth, deregulated DISC1-associated signaling pathways, and reduced synaptic densities in cultures composed of glutamatergic neurons. Cultures comprising a defined ratio of NGN2 and AD2 neurons then revealed considerably increased GABAergic synapse densities, which have not been observed in any iPSC-derived model so far. Increased inhibitory synapse densities could be associated with an increased efficiency of GABAergic differentiation, which we observed in AD2-transduced cultures of mutant neurons. Additionally, we found increased neuronal activity in GABAergic neurons through calcium imaging while the activity pattern of glutamatergic neurons remained unchanged.ConclusionsIn conclusion, our results demonstrate phenotypic differences in a co-culture comprising a defined ratio of DISC1 mutant NGN2 and AD2 neurons, as compared to culture models comprising only one neuronal cell type. Altered synapse numbers and neuronal activity imply that DISC1 impacts the excitatory/inhibitory balance in NGN2/AD2 co-cultures, mainly through increased GABAergic input.

Machine learning-based evaluation of spontaneous pain and analgesics from cellular calcium signals in the mouse primary somatosensory cortex using explainable features.

Pain that arises spontaneously is considered more clinically relevant than pain evoked by external stimuli. However, measuring spontaneous pain in animal models in preclinical studies is challenging due to methodological limitations. To address this issue, recently we developed a deep learning (DL) model to assess spontaneous pain using cellular calcium signals of the primary somatosensory cortex (S1) in awake head-fixed mice. However, DL operate like a "black box", where their decision-making process is not transparent and is difficult to understand, which is especially evident when our DL model classifies different states of pain based on cellular calcium signals. In this study, we introduce a novel machine learning (ML) model that utilizes features that were manually extracted from S1 calcium signals, including the dynamic changes in calcium levels and the cell-to-cell activity correlations. We focused on observing neural activity patterns in the primary somatosensory cortex (S1) of mice using two-photon calcium imaging after injecting a calcium indicator (GCaMP6s) into the S1 cortex neurons. We extracted features related to the ratio of up and down-regulated cells in calcium activity and the correlation level of activity between cells as input data for the ML model. The ML model was validated using a Leave-One-Subject-Out Cross-Validation approach to distinguish between non-pain, pain, and drug-induced analgesic states. The ML model was designed to classify data into three distinct categories: non-pain, pain, and drug-induced analgesic states. Its versatility was demonstrated by successfully classifying different states across various pain models, including inflammatory and neuropathic pain, as well as confirming its utility in identifying the analgesic effects of drugs like ketoprofen, morphine, and the efficacy of magnolin, a candidate analgesic compound. In conclusion, our ML model surpasses the limitations of previous DL approaches by leveraging manually extracted features. This not only clarifies the decision-making process of the ML model but also yields insights into neuronal activity patterns associated with pain, facilitating preclinical studies of analgesics with higher potential for clinical translation.

Transcranial Low-Intensity Focused Ultrasound Stimulation of the Visual Thalamus Produces Long-Term Depression of Thalamocortical Synapses in the Adult Visual Cortex.

Transcranial focused ultrasound stimulation (tFUS) is a noninvasive neuromodulation technique, which can penetrate deeper and modulate neural activity with a greater spatial resolution (on the order of millimeters) than currently available noninvasive brain stimulation methods, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). While there are several studies demonstrating the ability of tFUS to modulate neuronal activity, it is unclear whether it can be used for producing long-term plasticity as needed to modify circuit function, especially in adult brain circuits with limited plasticity such as the thalamocortical synapses. Here we demonstrate that transcranial low-intensity focused ultrasound (LIFU) stimulation of the visual thalamus (dorsal lateral geniculate nucleus, dLGN), a deep brain structure, leads to NMDA receptor (NMDAR)-dependent long-term depression of its synaptic transmission onto layer 4 neurons in the primary visual cortex (V1) of adult mice of both sexes. This change is not accompanied by large increases in neuronal activity, as visualized using the cFos Targeted Recombination in Active Populations (cFosTRAP2) mouse line, or activation of microglia, which was assessed with IBA-1 staining. Using a model (SONIC) based on the neuronal intramembrane cavitation excitation (NICE) theory of ultrasound neuromodulation, we find that the predicted activity pattern of dLGN neurons upon sonication is state-dependent with a range of activity that falls within the parameter space conducive for inducing long-term synaptic depression. Our results suggest that noninvasive transcranial LIFU stimulation has a potential for recovering long-term plasticity of thalamocortical synapses in the postcritical period adult brain.

Abstract WP293: Elucidating the Neuronal Basis of Diaschisis in Stroke Recovery

Numerous studies have shown that focal ischemic stroke changes cortical activity patterns, metabolism and blood flow not only in peri-infarct regions, but also in remote regions connected to the ischemic core. This phenomenon known as “diaschesis”, was predicted over 100 years ago and is presumed to play an important role in dictating the extent of stroke recovery. Although regional brain imaging studies provide some support to this idea (with caveats), direct examination of the structure and function of neurons connected to neurons lost in the infarct core, has not been adequately addressed. One reason for our lack of a detailed understanding is the methodologies to trace connected neurons and track their function/activity patterns over weeks and months time after stroke, did not exist until recently. To address this issue, we injected adeno-associated virus (AAV) into the adult mouse primary forelimb somatosensory cortex (FLS1) 2-3 weeks before induction of photothrombotic stroke. These AAVs could either be transported in a retrograde fashion to label neural inputs to the FLS1 (retro pAAV.CAG.GFP), or conversely move in an anterograde, trans-synaptic manner (AAV.Syn.Cre) to label neurons downstream of FLS1 neurons, such as in motor cortex. In the latter case, we utilized a transgenic mouse that co-expressed a cre-recombinase dependent fluorescent reporter (tdTomato), as well as a genetically encoded calcium sensor (GCaMP6s) in neurons. These dual reporters (tdTomato and GCaMP6s) allowed us to examine changes in dendritic structure as well as functional activity patterns in downstream motor neurons. Our initial findings using confocal microscopy to assess dendritic structure, indicate subtle changes in spine density in neuronal inputs and outputs of the FLS1, within the first week after stroke. Repeated in vivo imaging of calcium transients in downstream motor cortex neurons in awake mice before and after FLS1 cortex stroke, suggested a long lasting disruption in neuronal and ensemble activity patterns. These preliminary findings provide direct evidence that neurons in remotely connected brain regions suffer long-lasting impairments after stroke, thereby providing another potential target or substrate for future therapeutics to consider.

A ubiquitous spectrolaminar motif of local field potential power across the primate cortex

The mammalian cerebral cortex is anatomically organized into a six-layer motif. It is currently unknown whether a corresponding laminar motif of neuronal activity patterns exists across the cortex. Here we report such a motif in the power of local field potentials (LFPs). Using laminar probes, we recorded LFPs from 14 cortical areas across the cortical hierarchy in five macaque monkeys. The laminar locations of recordings were histologically identified by electrolytic lesions. Across all areas, we found a ubiquitous spectrolaminar pattern characterized by an increasing deep-to-superficial layer gradient of high-frequency power peaking in layers 2/3 and an increasing superficial-to-deep gradient of alpha-beta power peaking in layers 5/6. Laminar recordings from additional species showed that the spectrolaminar pattern is highly preserved among primates—macaque, marmoset and human—but more dissimilar in mouse. Our results suggest the existence of a canonical layer-based and frequency-based mechanism for cortical computation.

In vivo calcium imaging shows that satellite glial cells have increased activity in painful states.

Satellite glial cells are important for proper neuronal function of primary sensory neurons for which they provide homeostatic support. Most research on satellite glial cell function has been performed with in vitro studies, but recent advances in calcium imaging and transgenic mouse models have enabled this first in vivo study of single-cell satellite glial cell function in mouse models of inflammation and neuropathic pain. We found that in naïve conditions, satellite glial cells do not respond in a time-locked fashion to neuronal firing. In painful inflammatory and neuropathic states, we detected time-locked signals in a subset of satellite glial cells, but only with suprathreshold stimulation of the sciatic nerve. Surprisingly, therefore, we conclude that most calcium signals in satellite glial cells seem to develop at arbitrary intervals not directly linked to neuronal activity patterns. More in line with expectations, our experiments also revealed that the number of active satellite glial cells was increased under conditions of inflammation or nerve injury. This could reflect the increased requirement for homeostatic support across dorsal root ganglion neuron populations, which are more active during such painful states.

A critical review of ethanol effects on neuronal firing: A metabolic perspective.

Ethanol metabolism is relatively understudied in neurons, even though changes in neuronal metabolism are known to affect their activity. Recent work demonstrates that ethanol is preferentially metabolized over glucose as a source of carbon and energy, and it reprograms neurons to a state of reduced energy potential and diminished capacity to utilize glucose once ethanol is exhausted. Ethanol intake has been associated with changes in neuronal firing and specific brain activity (EEG) patterns have been linked with risk for alcohol use disorder (AUD). Furthermore, a haplotype of the inwardly rectifying potassium channel subunit, GIRK2, which plays a critical role in regulating excitability of neurons, has been linked with AUD and shown to be directly regulated by ethanol. At the same time, overexpression of GIRK2 prevents ethanol-induced metabolic changes. Based on the available evidence, we conclude thatthe mechanisms underlying the effects of ethanol on neuronal metabolism are a novel target for developing therapies for AUD.

Non-canonical interplay between glutamatergic NMDA and dopamine receptors shapes synaptogenesis

Direct interactions between receptors at the neuronal surface have long been proposed to tune signaling cascades and neuronal communication in health and disease. Yet, the lack of direct investigation methods to measure, in live neurons, the interaction between different membrane receptors at the single molecule level has raised unanswered questions on the biophysical properties and biological roles of such receptor interactome. Using a multidimensional spectral single molecule-localization microscopy (MS-SMLM) approach, we monitored the interaction between two membrane receptors, i.e. glutamatergic NMDA (NMDAR) and G protein-coupled dopamine D1 (D1R) receptors. The transient interaction was randomly observed along the dendritic tree of hippocampal neurons. It was higher early in development, promoting the formation of NMDAR-D1R complexes in an mGluR5- and CK1-dependent manner, favoring NMDAR clusters and synaptogenesis in a dopamine receptor signaling-independent manner. Preventing the interaction in the neonate, and not adult, brain alters in vivo spontaneous neuronal network activity pattern in male mice. Thus, a weak and transient interaction between NMDAR and D1R plays a structural and functional role in the developing brain.