Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. The entorhinal cortex (Ent) is among the earliest affected regions, and its neuropeptide cholecystokinin (CCK) supports neocortical-associated memory. Although our previous work demonstrated that CCK treatment rescues cognition and neuroplasticity in aged AD mice, the correlations among CCK expression, synaptic function, and cognitive decline with aging remain poorly understood. Using 3xTg-AD mice (2-18 months), we performed stereological, histological, and molecular analyses to evaluate brain atrophy, neuronal loss, glial responses, and gene expression. Cognitive function was assessed using the novel object recognition test (NOR), motor learning was evaluated using the rotarod test, and synaptic integrity was measured via electrophysiological recordings. We also investigated the therapeutic potential of CCK-B receptor (CCK-BR) agonists on learning and memory and neuroplasticity across disease stages of AD. In 3xTg-AD mice, the Ent exhibits significant atrophy and excitatory neuronal loss as early as 7 months of age, confirming its role as one of the earliest and most severely affected regions in AD. CCK was downregulated earlier than other synaptic genes in the Ent and other brain regions. Cholecystokinin tetrapeptide (CCK-4) treatment rescued deficits in synaptic plasticity, cognition, and motor learning in 3xTg-AD mice across multiple disease stages. Long-term administration of HT-267, a CCK-BR agonist with a prolonged half-life, in young 3xTg-AD mice delayed cognitive decline, enhanced synaptic scaffolding, and restored long-term potentiation in both the cortex and hippocampus (HPC). Our findings identify CCK downregulation as an early biomarker in AD and demonstrate the therapeutic effects of CCK-BR agonists in mitigating cognitive and synaptic deficits from mild to severe disease stages. The ability of long-term CCK-4 analogue treatment to decelerate AD progression indicates its promise as an early intervention strategy.

Video temporal grounding (VTG), which localizes the start and end times of a queried event in an untrimmed video, is a key test of whether multimodal large language models (MLLMs) understand not only what happens but also when it happens. Although modern MLLMs describe video content fluently, their timestamp predictions remain unreliable, while existing remedies either require costly post-training on temporal annotations or rely on coarse training-free heuristics. In this work, we probe the cross-modal attention of MLLMs and uncover a perception-generation gap. Our key finding is that MLLMs often know the target interval during prefill, but lose this signal when generating the final answer. In the prefill stage, a sparse set of attention heads, which we call Temporal Grounding Heads (TG-Heads), concentrates query-to-video attention on the ground-truth interval. During autoregressive decoding, however, the answer tokens shift attention away from this interval toward visually salient but query-irrelevant segments. This observation motivates an inference-time read-then-regenerate framework. We first convert TG-Head prefill attention into a debiased frame-level relevance signal and extract the high-attention interval it highlights. We then re-invoke the MLLM with visual context restricted to this interval, using video cropping or attention masking to suppress distractors. Without parameter updates and architectural changes, our framework consistently improves MiMo-VL-7B, Qwen3-VL-8B, and TimeLens-8B on three VTG benchmarks, with gains of up to +3.5 mIoU. The project website can be found at https://ddz16.github.io/mllmsknowwhen.github.io/.

The intricate cortical folds of large primates physically restrict access to substantial portions of neural information via interface devices. Here, we develop a bioelectronic system, sFlex-Fold, with switchable flexibility, representing the neural interface capable of nondestructive three-dimensional (3D) access to both cortical gyri and sulci, providing large-area, nonpenetrative deep tissue coverage. sFlex-Fold is based on an artificial intelligence (AI)-designed liquid metal alloy (LM-alloy), leveraging the phase change of the tailor-made LM-alloy to create neural interfacing electronics with tunable mechanical response to temperatures ranging from 25° to 37°C. The LM-alloy can be patterned into arbitrary circuit layouts with an ~10-micrometer resolution. The flexibility switching happens at the LM melting point, fine-tuned to 36.2°C, upon in vivo tissue contact, causing a three-order-of-magnitude reduction in the effective modulus of the implanted device. As a result, sFlex-Fold has the unique advantages of both a rigid and flexible state and can be morphed into complex, folded, 3D shapes. This enables nondestructive in vivo implantation into deep cortical sulci while maintaining large coverage (>80 square centimeters) over curved brain surfaces with tissue-matching mechanical compliance. Such 3D structural and mechanical mimicking enables high-quality electrical interfacing as quantitatively assessed using rodent and porcine models.

High-frequency stimulation (HFS)-induced long-term potentiation (LTP) is generally regarded as a homosynaptic Hebbian-type LTP, where synaptic changes are thought to occur at the synapses that project from the stimulation site and terminate onto the neurons at the recording site. In this study, we first investigated HFS-induced LTP on urethane-anesthetized rats and found that cortical HFS enhances neural responses at the recording site through the strengthening of local connectivity with nearby neurons at the stimulation site rather than through synaptic strengthening at the recording site. This enhanced local connectivity at the stimulation site leads to increased output propagation, resulting in signal potentiation at the recording site. Additionally, we discovered that HFS can also nonspecifically strengthen distant afferent synapses at the HFS site, thereby expanding its impact beyond local neural connections. This form of plasticity exhibits a neo-Hebbian characteristic as it exclusively manifests in the presence of cholecystokinin release, induced by HFS. The cortical HFS-induced local LTP was further supported by a behavioral task, providing additional evidence. Our results unveil a previously overlooked mechanism underlying cortical plasticity: synaptic plasticity is more likely to occur around the soma site of strongly activated cortical neurons rather than solely at their projection terminals.

Studies have demonstrated that NMDA receptors (NMDARs) mediate multiple forms of synaptic plasticity, including the induction of long-term potentiation (LTP) and long-term depression (LTD) [1] . The NR2A subunit is closely associated with LTP generation, which in turn induces learning and memory-related behaviors. This is evidenced by the significant memory deficit behaviors observed in NR2A knockout (NR2A -/-) mice [2] . Consequently, NR2A-KO animals serve as a valuable model for exploring memory encoding-related pathways and mechanisms, as well as for providing insights into drug-based treatments for memory disorders. Previous research has shown that cholecystokinin (CCK)-expressing neurons are abundantly present in the cerebral cortex and hippocampus, and they are involved in memory engram functions across multiple brain regions [3–6] . However, it remains unclear whether CCK administration can ameliorate the memory deficits exhibited by NR2A knockout animals in certain learning and memory behaviors. In this study, the novel object recognition task and auditory paired conditioned fear learning paradigm were employed to evaluate the role of CCK in rescuing memory deficits in NR2A knockout (NR2A-KO) mice. Our results revealed that NR2A-KO mice displayed significant impairments in both the novel object recognition paradigm and the conditioned fear behavioral paradigm. Notably, CCK administration improved the performance of these mice in these behavioral tasks. Concurrently, in vitro multichannel electrophysiological recordings were used to investigate the effects of CCK administration on LTP induction in the cortex and hippocampus. The findings indicated that CCK restored the loss of LTP in the cortex and hippocampus of NR2A-KO mice. Furthermore, fiber photometry was utilized to monitor calcium (Ca²⁺) activity in the auditory cortex (AC) in response to the auditory cue of paired conditioned fear. The results showed that CCK administration significantly enhanced calcium signal changes in the auditory cortex in response to the sound, suggesting that CCK treatment restored the memory of auditory paired conditioned fear in NR2A-KO mice to the level of wild-type mice. To verify the hypothesis that NR2A deficiency may affect CCK release from CCK neurons, building on our previous studies which showed that the projection of CCK neurons from the lateral entorhinal cortex (LEC) to the auditory cortex is involved in sound - cued associative memory [7, 8] , we employed a specific CCKBR sensor system combined with optogenetic viruses. We examined CCK release from CCK axon terminals projecting from the LEC to the AC following high - frequency stimulation in the presence of an NR2A antagonist. The results demonstrated that the NR2A antagonist blocked CCK release. Anatomically, a large number of NMDARs composed of NR2A subunits were found to be clustered at the CCK axon terminals projecting from the LEC to the AC, which structurally verified the possibility that NR2A might affect CCK release. Collectively, these results indicate that CCK administration not only compensates for the loss of LTP in NR2A-KO mice but also ameliorates certain memory deficit - like behaviors exhibited by these animals. Overall, our study suggests that CCK is a potential target for the treatment of memory deficits and clarifies its therapeutic role in the memory deficit behaviors displayed by NR2A-KO animals.

High frequency deep brain stimulation (DBS) is widely used for improving motor capability in patients with Parkinson's disease (PD). Here, an upconversion-based strategy is described for remote deep brain modulation, which is an all-optical solution for treating PD in rodent animals without any tethering interferences. It is demonstrated that both high frequency stimulation and inhibition of subthalamic nucleus (STN), can improve the motor function of Hemi-Parkinsonian rodent models, potentially providing a specific and flexible therapeutic alternative for treating PD. A multi-modal approach is further taken that combines optogenetics and electrophysiology recording, and found that high frequency optogenetic inhibition of STN work similarly as high frequency activation to rescue the pathologic electrical activity in the motor cortex and restore the motor deficiency in Hemi-Parkinsonian rodents. It is also shown that indirect inhibitory modification of entopeduncular nucleus (EP) within the basal ganglia system, which is induced by either STN inhibition or activation, plays a critical role in the STN-DBS induced therapeutic effects in the Hemi-Parkinsonian animals. These results provide first experimental evidence supporting a working principle of STN-DBS by disruption of anterograde signal transmission along the indirect pathway of basal ganglia, and can be instructive for future clinical treatment of PD with DBS.

BACKGROUND:The stigmatisation of mental illness is affected by culture, beliefs, and empathy; however, researchers rarely take these factors into consideration when developing interventions to reduce stigma. Nursing professionals represent the largest group of healthcare workers globally and are responsible for the care and recovery of individuals with schizophrenia. However, people with schizophrenia face serious stigmatisation. Studies findings show that nursing students express unfavourable attitudes towards people with schizophrenia, indeed more severely than medical students express such attitudes. As nursing students are future healthcare providers for individuals with schizophrenia, addressing their existing stigmas is essential for providing high-quality care for people with schizophrenia. METHODS:The study was a single-center, two-arm, parallel, open-label, pilot randomized controlled trial conducted in a hospital without a psychiatry department. The study intervention was implemented online from February 20, 2023 to June 20, 2023. Sixty fourth-year nursing students were included according to this study's inclusion criteria through convenience sampling and randomised into the experimental and control groups equally. The intervention training program was developed through a systematic review, focus group interviews with nursing students, expert panel, and consultation with nursing students. The experimental group received a 4-week intervention training program, whereas the control group received instructions to read a book. The feasibility and acceptability were assessed. The efficacy of the intervention was evaluated by the Knowledge about Schizophrenia Test (KAST), the Mental Illness Clinicians' Attitudes Scale (MICA), the Reported and Intended Behavior Scale (RIBS), and the Jefferson Scale of Empathy (JSE) at baseline (T1), post-intervention (T2), and 3-month follow-up (T3). The analyses included paired T-tests, chi-square tests for nominal variables, Wilcoxon signed-rank tests, and generalized estimating equations (GEE). RESULTS:The recruitment, retention, and intervention attendance rates indicate that the intervention was both feasible and acceptable. The experimental group showed significant improvements in KAST scores (knowledge of schizophrenia) at T2 and T3, along with notable improvements in the RIBS score (intended behaviour) at T2 and a significant decrease in the MICA score (negative attitudes) at T2 and T3. Furthermore, there was a significant increase in JSE-NSR score (empathy) at T3. The control group displayed no significant changes in the MICA, RIBS or JSE-NSR scores at T2 and T3. GEE test showed that the experimental group had a more significant decrease in MICA scores at T2 and T3, a substantial enhancement in JSE score at T3 and a more significant decrease in RIBS at T2 compared to the control group. CONCLUSION:The results of this study revealed that the Chinese culture-specific online intervention was both feasible and well-received among fourth-year nursing students for reducing schizophrenia stigma. TRIAL REGISTRATION:The study was prospectively registered at ClinicalTrials.gov (Identifier: NCT05413408) on 10 June 2022. https://www. CLINICALTRIALS:gov/study/NCT05413408?term=MICA&rank=10 .

Emerging evidence highlights the cerebellum’s involvement in Parkinson’s disease (PD), yet its intrinsic functional connectivity with cortical-subcortical networks remains largely unexplored. This study aims to investigate cerebellar functional network alterations in PD and their associations with motor, cognitive, and emotional symptoms, as well as age-related effects. 82 participants with PD (PwPD) and 38 healthy controls (HCs) underwent structural and resting-state functional MRI scans. We conducted volumetric analysis in the cerebellum and examined the involvement of cerebellar functional networks in PD, both within-network and between-network connections regarding cortical-subcortical large-scale networks. Additionally, we explored correlations with motor, cognitive, and emotional symptoms, as well as age-related associations in PwPD. No significant differences in cerebellar volume were observed between PwPD and HCs. PwPD exhibited reduced functional connectivity within the cerebellar network and between the cerebellum (CER) and the salience network (SN) (P < 0.001). Decreased CER-SN connectivity correlated with lower MoCA scores and higher HAMD scores, indicating associations with cognitive impairment and depressive symptoms. Additionally, CER-MTL (medial temporal lobe) connectivity positively correlated with both HAMD and HAMA scores in PwPD. Age-related differences in CER-SN connectivity were significant between PwPD and HCs (P = 0.008). Our study suggests the involvement of cerebellar large-scale functional network connectivity in PD, emphasizing the role of cerebellar functional networks in the emotional and cognitive aspects of PD. Our study revealed significant reductions in functional connectivity both within the cerebellum and between the cerebellum and specific cortical-subcortical networks in Parkinson’s Disease (PD). Moreover, these intricate connections between the cerebellum and distinct functional networks exhibit associations with cognitive and emotional symptoms in PD. Our findings collectively propose that the altered functional connections of the cerebellum, particularly with multiple large-scale cortical networks, could hold a pivotal role in information processing across fundamental neurocognitive functions in PD. These insights carry significant implications for advancing the diagnosis and treatment of Parkinson’s Disease, presenting a promising avenue for targeted therapeutic interventions.

It has been well established that Cornu Ammonis-(CA1) and subiculum (SUB) serve as the major output components of the entorhinal-hippocampal circuitry. Nevertheless, how the neuromodulators regulate the neurocircuitry in hippocampal formation has remained elusive. Cholecystokinin (CCK), is the most abundant neuropeptide in the central nervous system, which broadly regulates the animal’s physiological status at multiple levels, including neuroplasticity and its behavioral consequences. Here, we uncover that exogenous CCK potentiates the excitatory synaptic transmission in the CA1-SUB projections via CCK-B receptor. Dual-color light theta burst stimulation elicits heterosynaptic long-term potentiation in distal SUB region. Light activation of medial entorhinal cortex (MEC) derived CCK-positive neurons triggers the CCK release in the SUB. Neuronal activities of SUB-projecting MECCCK neurons are necessary for conveying and processing of navigation-related information. In conclusion, our findings prove a crucial role of CCK in regulating neurobiological functions in the SUB region. Cholecystokinin derived from the medial entorhinal cortex modulates heterosynaptic plasticity in the CA1-subiculum pathway and regulates navigation-related information in wild-type mice.

Background: Recall of specific events, which is known as episodic memory, relies heavily on synaptic plasticity in the hippocampus. Molecular and cellular processes that mediate this phenomenon are intricate and include neuronal and glial functions, signaling pathways, and synaptic reorganization. Objective: This work will address the molecular and cellular aspects of synaptic plasticity in the hippocampus and its role in the formation of episodic memories through processes including dendritic spine remodelling, astrocytes and microglia, and epigenetics. Methodology: Literature review of recent findings and theoretical frameworks such as Morris’s neurobiological theory of the hippocampus was done to synthesize the molecular markers, signaling pathways, and neuromodulation. Experimental data regarding the involvement of calcium signaling, synaptic tagging, and protein synthesis dependent long-term potentiation (LTP) in memory formation were reviewed. Results: This paper discusses how calcium influx, CaMKII activation and CREB-mediated transcription contribute to the preservation of LTP. Dendritic spine remodeling is highlighted as a key structural process and astrocytes and microglia are identified to regulate synaptic plasticity and neural circuit function. Moreover, epigenetic mechanisms, such as histone acetylation and DNA methylation, relate synaptic activity to the expression of genes associated with memory. Conclusion: Results of this study explain the molecular and cellular mechanisms of hippocampal synaptic plasticity and the formation of episodic memory. These findings provide a basis for future research on potential treatment for memory related diseases and underscore the significance of molecular biology in cognitive neuroscience.

Neuronal interactions between inhibitory and excitatory neurons play a pivotal role in regulating the balance of excitation and inhibition in the central nervous system (CNS). Consequently, the efficacy of inhibitory/excitatory synapses profoundly affects neural network processing and overall neuronal functions. Here, we describe a novel form of long-term potentiation (LTP) induced at cortical inhibitory synapses and its behavioral consequences. We show that high-frequency laser stimulation (HFLS) of GABAergic neurons elicit inhibitory LTP (i-LTP) in pyramidal neurons of the auditory cortex (AC). The selective activation of cholecystokinin-expressing GABA (GABACCK) neurons is essential for the formation of HFLS-induced i-LTP, rather than the classical parvalbumin (PV) neurons and somatostatin (SST) neurons. Intriguingly, i-LTP can be evoked in the AC by adding the exogenous neuropeptide CCK when PV neurons and SST neurons are selectively activated in PV-Cre and SST-Cre mice, respectively. Additionally, we discovered that low-frequency laser stimulation (LFLS) of PV neurons paired with HFLS of GABACCK neurons potentiates the inhibitory effect of PV interneurons on pyramidal neurons, thereby generating heterosynaptic i-LTP in the AC. Notably, light activation of GABACCK neurons in CCK-Cre mice significantly attenuates sound- shock associative memory, while stimulation of PV neurons does not affect this memory in PV-Cre mice. In conclusion, these results demonstrate a critical mechanism regulating the excitation-inhibition balance and modulating learning and memory in cortical circuits. This mechanism might serve as a potential target for the treatment of neurological disorders, including epilepsy and Alzheimer’s disease.

Studies have shown that NMDA receptors (NMDARs) can mediate multiple forms of synaptic plasticity, including induction of long-term enhancement (LTP) or long- term inhibition (LTD)[1]. The NR2A subunit has a strong correlation with LTP production and can in turn induce learning-related behaviors. For example, NR2A knockout (NR2A-/-) mice exhibit some significant memory-deficit behaviors[2]. Therefore, it can be used as a valuable model for exploring the pathways and mechanisms involved in memory encoding and may also inform the treatment of memory disorders. The cholecystokinin (CCK) neuronal ensemble has been shown to be involved in memory imprinting function in multiple brain regions[3–6]. However, it remains unclear whether pharmacological modulation of CCK can improve memory- related deficits in NR2A knockout animals. This study utilizes a novel object recognition task and a context-dependent fear learning paradigm to evaluate the role of CCK in memory generalization in NR2A-KO mice. Our results show that NR2A- KO mice exhibit significantly impaired discrimination, learning, and fear conditioning. Notably, CCK manipulation enhanced the associative memory generalization and discrimination abilities of these animals. Similarly, we performed electrophysiological studies, including in vitro multichannel recordings, to examine the effects of CCK on LTP-induction in the cortex and hippocampus. Notably, CCK restored LTP in the cortex and hippocampus in NR2A-KO mice. In addition, monitoring of calcium (Ca2+) activity during memory recall using fiber photometry in the auditory cortex (AC) showed a significant enhancement of calcium signal after CCK administration. To test our hypothesis that the deletion of NR2A may affect the release of CCK, we used a specific CCKBR sensor system combined with optogenetic viruses to detect the release of CCK after high-frequency stimulation of the CCK axon terminus projected by LEC to AC, but the release of CCK was blocked by the application of NR2A antagonists. These results suggest that CCK not only compensates for the loss of LTP in NR2A-KO mice, but also improves the corresponding memory-deficit- like behavior in animals. Overall, our findings identify CCK as a promising target for the treatment of memory deficits and elucidate its role in memory encoding mechanisms.

The thalamocortical pathways exhibit neuroplasticity not only during the critical period but also in adulthood. In this study, we investigated how cholecystokinin (CCK) modulates age-dependent thalamocortical plasticity. Our findings demonstrated that CCK is expressed in thalamocortical neurons and that high-frequency stimulation (HFS) of the thalamocortical pathway triggers the release of CCK in auditory cortex (ACx), as detected by a CCK sensor. HFS of the medial geniculate body (MGB) induced thalamocortical long-term potentiation (LTP) in wild-type young adult mice. However, knockdown of CCK expression in MGB neurons or blockade of the CCK-B receptor (CCKBR) in the ACx abolished HFS-induced LTP. Interestingly, this LTP could not be elicited in juvenile (3-week-old) or aged mice (over 18-month-old) due to distinct mechanisms: the absence of CCKBR in juveniles and the inability to release CCK in aged mice. Notably, exogenous administration of CCK into the ACx rescued LTP in aged mice and significantly improved frequency discrimination. These findings highlight the potential of CCK as a therapeutic intervention for ameliorating neuroplasticity deficits associated with thalamocortical connectivity.

Intracortical brain-computer interfaces (iBCIs) promise revolutionary clinical and research applications. State-of-the-art iBCIs rely on high-density (HD) microelectrode arrays (MEAs) to sense massive neuronal populations. However, HD MEAs are bandwidth-demanding, posing a significant challenge for wireless iBCIs. Prior iBCI systems have relied on compression to reduce neural signal bitrate. Unfortunately, existing schemes are blind to neurons' signal characteristics, resulting in poor compression efficiency and severe degradation in iBCI performance. This paper explores a neuron-aware approach to the design of efficient brain-to-computer communication systems. We present NeuroZip, a neural signal compression scheme that significantly reduces bitrate without compromising neural features, enabling various wireless iBCI applications to track neurons under limited bandwidth. To achieve this, NeuroZip first models and analyzes the complex feature space of HD neural signals, and then embraces neuron-awareness into an efficient genetic search algorithm that can quickly converge to an optimal compression strategy despite the large solution space yielded by HD MEA's high microelectrode count. Preliminary experiments conducted on real neural datasets show that, compared to neuron-blind schemes, NeuroZip reduces bandwidth by up to 2.2x under the same error constraint, or reduces error rate by up to 8x under the same bandwidth. Further experiments demonstrate NeuroZip imposes minimal impacts on downstream iBCI tasks, limiting the increase of error rate within 2.4% for three representative iBCI applications.

Epilepsy is a disorder characterized by an imbalance between excitability and inhibition, leading to uncontrolled hyperexcitability of neurons in the central nervous system. Despite the prevalence of epileptic seizures, the underlying mechanisms driving this hyperexcitability remain poorly understood. This review article aims to enhance our understanding of the mechanisms of epilepsy, with a specific focus on the role of cholecystokinin (CCK) in this debilitating disease. We will begin with an introduction to the topic, followed by an examination of the role of GABAergic neurons and the synaptic plasticity mechanisms associated with seizures. As we delve deeper, we will elucidate how CCK and its receptors contribute to seizure behavior. Finally, we will discuss the CCK-dependent synaptic plasticity mechanisms and highlight their potential implications in seizure activity. Through a comprehensive examination of these aspects, this review provides valuable insights into the involvement of CCK and its receptors in epilepsy. By improving our understanding of the mechanisms underlying this condition, particularly the role of CCK, we aim to contribute to the development of more effective treatment strategies.

Cholecystokinin (CCK) has been confirmed to be essential in NMDA-dependent long-term potentiation (LTP) at mouse cortical synapses. This paper has proven that CCK is necessary for LTP induced by high-frequency stimulation of mouse hippocampal synapses projected from the entorhinal cortex. We show that the subunit of the axonal NMDA receptor dominant modulates the activity-induced LTP by triggering pre-synaptic CCK release. A functional pre-synaptic NMDA receptor is required to induce LTP mediated by the axonal Ca2+ elevation and CCK exocytosis at CCK-specific neurons. Genetic depletion of the GluN1 subunit of NMDA receptors on CCK neurons, which projected from the entorhinal cortex largely abolished the axonal Ca2+ elevation and disturbed the secretion of CCK in hippocampus. These results demonstrate that activity-induced LTP at the hippocampal synapse is CCK-dependent, and CCK secretion from the axonal terminal is modulated by pre-synaptic NMDA receptors.image

Despite the great success achieved by recently developed neural interfaces, multi-site monitoring and regulating neural activities with high spatial and temporal selectivity remain a challenge. Here, an implantable, remotely controllable, fiber-based ferromagnetic system permitting 3D navigation, omnidirectional steering, multiplexing neural recording, and modulation is presented. A family of fibers is fabricated that allows for the heterogeneous integration of ferromagnetic, optical, microfluidic, electrical, and electrochemical components into the proposed multifunctional neural interface. Coupling with magnetic actuation, it is demonstrated that this system can enable optical and chemical modulation of local neural activities across multiple distant regions in rodent brains, while simultaneously allowing the real-time monitoring of neural electrophysiological and chemical activities. Furthermore, to systematically identify altered patterns of behaviors, brain activities and dopamine release during optogenetic modulation of specific nuclei in Parkinsonian animals this platform is employed. This proposed system with high spatial selectivity, multiplexing sensing and multimodal manipulating capabilities offers a versatile platform to advance both fundamental neuroscience studies and translational applications in neurologic disease treatments. An implantable, remotely controllable, fiber-based ferromagnetic system capable of three-dimensional navigation, omnidirectional steering, multiplexed neural recording and modulation is developed. Coupling with magnetic actuation, its functionality, stability and biocompatibility for multiplexed electrical recording and modulation of distinct neuron populations in the rodent brains are successfully demonstrated in this study. image

Cholecystokinin (CCK) plays a key role in various brain functions, including both health and disease states. Despite the extensive research conducted on CCK, there remain several important questions regarding its specific role in the brain. As a result, the existing body of literature on the subject is complex and sometimes conflicting. The primary objective of this review article is to provide a comprehensive overview of recent advancements in understanding the central nervous system role of CCK, with a specific emphasis on elucidating CCK's mechanisms for neuroplasticity, exploring its interactions with other neurotransmitters, and discussing its significant involvement in neurological disorders. Studies demonstrate that CCK mediates both inhibitory long-term potentiation (iLTP) and excitatory long-term potentiation (eLTP) in the brain. Activation of the GPR173 receptor could facilitate iLTP, while the Cholecystokinin B receptor (CCKBR) facilitates eLTP. CCK receptors' expression on different neurons regulates activity, neurotransmitter release, and plasticity, emphasizing CCK's role in modulating brain function. Furthermore, CCK plays a pivotal role in modulating emotional states, Alzheimer's disease, addiction, schizophrenia, and epileptic conditions. Targeting CCK cell types and circuits holds promise as a therapeutic strategy for alleviating these brain disorders.

The hippocampus is a crucial brain region involved in the process of forming and consolidating memories. Memories are consolidated in the brain through synaptic plasticity, and a key mechanism underlying this process is called long-term potentiation (LTP). Recent research has shown that cholecystokinin (CCK) plays a role in facilitating the formation of LTP, as well as learning and memory consolidation. However, the specific mechanisms by which CCK is involved in hippocampal neuroplasticity and memory formation are complicated or poorly understood. This literature review aims to explore the role of LTP in memory formation, particularly in relation to hippocampal memory, and to discuss the implications of CCK and its receptors in the formation of hippocampal memories. Additionally, we will examine the circuitry of CCK in the hippocampus and propose potential CCK-dependent mechanisms of synaptic plasticity that contribute to memory formation.

In the preclinical translational studies, drug candidates with remarkable anti-epileptic efficacy demonstrate long-term suppression of spontaneous recurrent seizures (SRSs), particularly convulsive seizures (CSs), in mouse models of chronic epilepsy. However, the current methods for monitoring CSs have limitations in terms of invasiveness, specific laboratory settings, high cost, and complex operation, which hinder drug screening efforts. In this study, a camera-based system for automated detection of CSs in chronically epileptic mice is first established to screen potential anti-epilepsy drugs.