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Inhibition of a cortico-thalamic circuit attenuates cue-induced reinstatement of drug-seeking behavior in "relapse prone" male rats.

RATIONALE: Relapse often occurs when individuals are exposed to stimuli or cues previously associated with the drug-taking experience. The ability of drug cues to trigger relapse is believed to be a consequence of incentive salience attribution, a process by which the incentive value of reward is transferred to the reward-paired cue. Sign-tracker (ST) rats that attribute enhanced incentive value to reward cues are more prone to relapse compared to goal-tracker (GT) rats that primarily attribute predictive value to such cues. OBJECTIVES: The neurobiological mechanisms underlying this individua

Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine-associated memories in mice.

In drug addiction, environmental stimuli previously associated with cocaine use readily elicit cocaine-associated memories, which persist long after abstinence and trigger cocaine craving and consumption. Although previous studies suggest that the medial prefrontal cortex (mPFC) is involved in the expression of cocaine-addictive behaviors, it remains unclear whether excitatory and inhibitory neurons in the mPFC are causally related to the formation and retrieval of cocaine-associated memories. To address this issue, we used the designer receptors exclusively activated by designer drugs (DREADD

Effect of Painful Stimuli on PVN CRH Neurons: Implications for States of Consciousness Under Isoflurane Anesthesia.

BACKGROUND: Many patients undergoing surgery experience accompanying pain symptoms preoperatively. The impact of painful stimuli on general anesthesia remains largely unknown. Corticotrophin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVN CRH neurons) are crucial central stress hubs that respond to painful stimuli. These neurons also participate in regulating processes such as sleep and anesthesia. Natural reward can inhibit PVN CRH neurons to relieve stress-induced behavioral changes, but the effect of natural reward on the anesthesia process in patients with

Cell types and neuronal genetic architecture in the rat CSF-contacting nucleus and the role of 5-HT in this nucleus in mediating morphine addiction through the brain-CSF circuit.

INTRODUCTION: To elucidate the cellular composition of the cerebrospinal fluid-contacting nucleus, establish a comprehensive gene expression database for this nucleus, and investigate its potential functional roles. METHODS: we used single-cell sequencing technology combined with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to characterize the transcriptional architecture of the CSF-contacting nucleus and elucidate its potential biological functions. Additionally, Conditioned place preference (CPP) testing, chemogenetic techniques, ELISA, and ultra-pe

Hcn1-dependent engram neurons in the PVN encode gastric inflammatory sensitization.

The brain encodes peripheral inflammatory signals, but the regulatory mechanism by which the brain controls gastric inflammation remains unclear. This study reveals a circuit through which Fos-positive neurons in the paraventricular nucleus of the hypothalamus (PVN) regulate gastritis via a PVN-dorsal motor nucleus of the vagus-stomach neural circuit and the hypothalamic-pituitary-adrenal (HPA) axis. Using activity-dependent genetic labeling, chemogenetics, and optogenetics, we demonstrate that FosPVN neurons are essential for gastritis progression and can be activated by stress to drive chron…

Circuit Reorganization of Subicular Cell-Type-Specific Interneurons in Temporal Lobe Epilepsy.

The subiculum represents a crucial brain pivot in regulating seizure generalization in temporal lobe epilepsy (TLE), primarily through a synergy of local GABAergic and long-projecting glutamatergic signaling. However, little is known about how subicular GABAergic interneurons are involved in a cell-type-specific way. Here, employing Ca2+ fiber photometry, retrograde monosynaptic viral tracing, and chemogenetics in epilepsy models of both male and female mice, we elucidate circuit reorganization patterns mediated by subicular cell-type-specific interneurons and delineate their functional dispar…

A neural circuit for the suppression of feeding under persistent pain.

In humans, persistent pain often leads to decreased appetite. However, the neural circuits underlying this behaviour remain unclear. Here, w … ompanied by decreased feeding behaviour in both males and females. Inhibition of this circuit using chemogenetics can alleviate the feeding suppression symptoms. Our study indicates that the GluACC → GluLHA → Arc circuit is involved in driving the suppression of feeding under persistent pain through POMC neuronal activity. This previously unrecognized pathway c …

Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation.

Astrocytes play crucial and diverse roles in brain health and disease. The ability to selectively control astrocytes provides a valuable tool for understanding their function and has the therapeutic potential to correct dysfunction. Existing technologies such as optogenetics and chemogenetics require the introduction of foreign proteins, which adds a layer of complication and hinders their clinical translation. A novel technique, magnetomechanical stimulation (MMS), that enables remote and selective control of astrocytes without genetic modification is described here. MMS exploits the mechanos…

Investigating the transition from recent to remote memory using advanced tools.

Remote memories, weeks to decades long, are usually the ones most important to the organism, as the longevity of a memory is tightly connect … gid as originally proposed. In this review we will focus on the integration of new methods, such as chemogenetics, optogenetics and calcium imaging, which enable genetic specificity as well as high temporal and spatial resolution. Using these methods, recent studies have started to resolve the inconsistencies of past findings by observing and manipulating neura …

Disruption of neonatal Purkinje cell function underlies injury-related learning deficits.

It is hypothesized that perinatal cerebellar injury leads to long-term functional deficits due to circuit dysmaturation. Using a novel integration of GCaMP6f fiber photometry with automated measurement of cerebellar behavior using the ErasmusLadder, we causally link cerebellar injury to altered Purkinje cell responses during maladaptive behavior. Chemogenetic inhibition of neonatal Purkinje cells is sufficient to phenocopy the effects of perinatal cerebellar injury. Our results uncover a direct link between perinatal cerebellar injury and activity-dependent maturation of cerebellar cortex.

How is Excitotoxicity Being Modelled in iPSC-Derived Neurons?

Excitotoxicity linked either to environmental causes (pesticide and cyanotoxin exposure), excitatory neurotransmitter imbalance, or to intri … th approaches to modelling excitotoxicity that include editing of disease-associated gene variants, chemogenetics, and environmental risk-associated exposures make iPSC primed to examine gene-environment interactions and disease-associated excitotoxic mechanisms. Critical to this is knowledge of which neurotransmitter receptor subunits are expressed by iPSC-der …

Hypothermia protects the integrity of corticospinal tracts and alleviates mitochondria injury after intracerebral hemorrhage in mice.

Disruption of corticospinal tracts (CST) is a leading factor for motor impairments following intracerebral hemorrhage (ICH) in the striatum. Previous studies have shown that therapeutic hypothermia (HT) improves outcomes of ICH patients. However, whether HT has a direct protection effect on the CST integrity and the underlying mechanisms remain largely unknown. In this study, we employed a chemogenetics approach to selectively activate bilateral warm-sensitive neurons in the preoptic areas to induce a hypothermia-like state. We then assessed effects of HT treatment on the integrity of CST and …

Cell-type-specific hypothalamic pathways to brainstem drive context-dependent strategies in response to stressors.

Adaptive behavioral responses to stressors are critical for survival. However, which brain areas orchestrate switching the appropriate stres … ed the involvement of the dorsomedial hypothalamus (DMH). Further investigation using optogenetics, chemogenetics, and photometry revealed that glutamatergic projections from the DMH to periaqueductal gray (PAG) mediated responses to inside stressors, while GABAergic projections, particularly from tachykinin1-expressing neurons, played a crucial role in coping …

Glutamatergic and GABAergic neurons in the vLGN mediate the nociceptive effects of green and red light on neuropathic pain.

Phototherapy is an emerging non-pharmacological treatment for depression, circadian rhythm disruptions, and neurodegeneration, as well as pain conditions including migraine and fibromyalgia. However, the mechanism of phototherapy-induced antinociception is not well understood. Here, using fiber photometry recordings of population-level neural activity combined with chemogenetics, we found that phototherapy elicits antinociception via regulation of the ventral lateral geniculate body (vLGN) located in the visual system. Specifically, both green and red lights caused an increase of c-fos in vLGN…

Латеральная новая кора критична для реконсолидации контекстуального страха.

Память — это продукт согласованной деятельности многих областей мозга. Дисрегуляция процессов консолидации и переработки меморных следов, кодирующих страховые переживания, может привести к страховым психопатологиям. Здесь мы оценили, как уже существующие памятные образы изменяются в результате опыта, особенно лабилизацию/реконсолидацию памяти, используя метод целенаправленного анализа всего мозга — позитронно-эмиссионную томографию у самцов мышей. Мы обнаружили различия в потреблении глюкозы в латеральной новой коре, гиппокампе и амгдале у мышей, проходящих лабилизацию/реконсолидацию процессов

Совпадение в аннотации оригинала
Memories are a product of the concerted activity of many brain areas. Deregulation of consolidation and reprocessing of mnemonic traces that … zation/reconsolidation processes compared to animals that did not reactivate a fear memory. We used chemogenetics to obtain insight into the role of cortical areas in these phases of memory and found that the lateral neocortex is necessary for fear memory reconsolidation. Inhibition of lateral neocortex during reconsolidation altered glucose consumption levels …

Silencing spinal interneurons inhibits immune suppressive autonomic reflexes caused by spinal cord injury.

Spinal cord injury (SCI) at high spinal levels (e.g., above thoracic level 5) causes systemic immune suppression; however, the underlying mechanisms are unknown. Here we show that profound plasticity develops within spinal autonomic circuitry below the injury, creating a sympathetic anti-inflammatory reflex, and that chemogenetic silencing of this reflex circuitry blocks post-SCI immune suppression. These data provide new insights and potential therapeutic options for limiting the devastating consequences of post-traumatic autonomic hyperreflexia and post-injury immune suppression.

The medial prefrontal cortex-ventral tegmental area dopaminergic circuit regulates the pleasure of tactile contact by releasing dopamine in the nucleus accumbens.

BACKGROUND AND PURPOSE: Tactile contact during social interactions is believed to enhance the experience of pleasure. Dopaminergic neurons i … as detected by immunofluorescence. A combination of behavioural tests, fibre-optic calcium imaging, chemogenetics, patch-clamp techniques and molecular biological methods were used to investigate the circuit mechanism mediating pleasure of tactile contact. KEY RESULTS: Dopaminergic neurons in the VTA were implicated in triggering pleasurable emotions associate …

Amylin Receptor Signalling in the Laterodorsal Tegmental Nucleus Controls Food Intake Through Projections to the Ventral Tegmental Area.

BACKGROUND: The role of amylin signalling in energy balance control has been understudied in calcitonin receptor (CTR) expressing nuclei such as the mesopontine laterodorsal tegmental nucleus (LDTg). Our lab has shown that LDTg amylin signalling reduces feeding and body weight, but the neuronal phenotype and downstream targets of LDTgCTR cells mediating these feeding effects remain unknown. Given that the LDTg has been established to modulate reward and motivated behaviours, we hypothesize that LDTg amylin signalling influences energy balance via direct modulation of VTA activity. MATERIALS A

Supramammillary projections to the lateral preoptic area drive dopamine release and active behavior.

UNLABELLED: The supramammillary nucleus (SuM) is known to promote active, approach-oriented behaviors by engaging ventral tegmental area (VTA) dopamine neurons projecting to the nucleus accumbens (NAc), primarily via a glutamatergic SuM→medial septum (MS) pathway. However, the role of other SuM projections in this process remains unclear. Here we combined anatomical tracing, fiber photometry, chemogenetic, and optogenetic approaches to investigate the SuM→lateral preoptic area (LPO) pathway. We found that SuM→LPO neurons possess extensive collateral projections and are inhibited during consumm

Astrocytes in the paraventricular nucleus mediates inflammation-related depression in mice treated with lipopolysaccharide.

BACKGROUND: Inflammation has been implicated in the pathogenesis of depression, yet the role of astrocytes in modulating these processes remains poorly understood. This study aimed to explore the involvement of paraventricular nucleus (PVN) astrocytes in inflammation-related depression, focusing on their impact on depression-like behaviors, neuronal activity, and immune responses. METHODS: We used the lipopolysaccharide (LPS)-induced depression model to evaluate depression-like behaviors in mice through sucrose preference, open field, and forced swim tests. Calcium dynamics in PVN astrocytes