Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22.375
Filtrar
1.
Neuropsychopharmacology ; 48(1): 168-185, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36180784

RESUMO

Emerging research on neuroplasticity processes in psychosis spectrum illnesses-from the synaptic to the macrocircuit levels-fill key gaps in our models of pathophysiology and open up important treatment considerations. In this selective narrative review, we focus on three themes, emphasizing alterations in spike-timing dependent and Hebbian plasticity that occur during adolescence, the critical period for prefrontal system development: (1) Experience-dependent dysplasticity in psychosis emerges from activity decorrelation within neuronal ensembles. (2) Plasticity processes operate bidirectionally: deleterious environmental and experiential inputs shape microcircuits. (3) Dysregulated plasticity processes interact across levels of scale and time and include compensatory mechanisms that have pathogenic importance. We present evidence that-given the centrality of progressive dysplastic changes, especially in prefrontal cortex-pharmacologic or neuromodulatory interventions will need to be supplemented by corrective learning experiences for the brain if we are to help people living with these illnesses to fully thrive.


Assuntos
Período Crítico Psicológico , Transtornos Psicóticos , Adolescente , Humanos , Plasticidade Neuronal/fisiologia , Aprendizagem/fisiologia , Neurônios/fisiologia
2.
Neuropsychopharmacology ; 48(1): 113-120, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35810199

RESUMO

Activity-dependent synaptic plasticity is a ubiquitous property of the nervous system that allows neurons to communicate and change their connections as a function of past experiences. Through reweighting of synaptic strengths, the nervous system can remodel itself, giving rise to durable memories that create the biological basis for mental function. In healthy individuals, synaptic plasticity undergoes characteristic developmental and aging trajectories. Dysfunctional plasticity, in turn, underlies a wide spectrum of neuropsychiatric disorders including depression, schizophrenia, addiction, and posttraumatic stress disorder. From a mechanistic standpoint, synaptic plasticity spans the gamut of spatial and temporal scales, from microseconds to the lifespan, from microns to the entire nervous system. With the numbers and strengths of synapses changing on such wide scales, there is an important need to develop measurement techniques with complimentary sensitivities and a growing number of approaches are now being harnessed for this purpose. Through hemodynamic measures, structural and tracer imaging, and noninvasive neuromodulation, it is possible to image structural and functional changes that underlie synaptic plasticity and associated behavioral learning. Here we review the mechanisms of neural plasticity and the historical and future trends in techniques that allow imaging of synaptic changes that accompany psychiatric disorders, highlighting emerging therapeutics and the challenges and opportunities accompanying this burgeoning area of study.


Assuntos
Saúde Mental , Plasticidade Neuronal , Humanos , Plasticidade Neuronal/fisiologia , Sinapses/fisiologia , Neurônios/fisiologia , Aprendizagem/fisiologia
4.
Neuropsychopharmacology ; 48(1): 191-208, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36198876

RESUMO

Transcranial magnetic stimulation (TMS) is a non-invasive technique for focal brain stimulation based on electromagnetic induction where a fluctuating magnetic field induces a small intracranial electric current in the brain. For more than 35 years, TMS has shown promise in the diagnosis and treatment of neurological and psychiatric disorders in adults. In this review, we provide a brief introduction to the TMS technique with a focus on repetitive TMS (rTMS) protocols, particularly theta-burst stimulation (TBS), and relevant rTMS-derived metrics of brain plasticity. We then discuss the TMS-EEG technique, the use of neuronavigation in TMS, the neural substrate of TBS measures of plasticity, the inter- and intraindividual variability of those measures, effects of age and genetic factors on TBS aftereffects, and then summarize alterations of TMS-TBS measures of plasticity in major neurological and psychiatric disorders including autism spectrum disorder, schizophrenia, depression, traumatic brain injury, Alzheimer's disease, and diabetes. Finally, we discuss the translational studies of TMS-TBS measures of plasticity and their therapeutic implications.


Assuntos
Transtorno do Espectro Autista , Estimulação Magnética Transcraniana , Adulto , Humanos , Estimulação Magnética Transcraniana/métodos , Plasticidade Neuronal/fisiologia , Encéfalo
5.
Neuropsychopharmacology ; 48(1): 21-36, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35577914

RESUMO

Over the last 15 years, the field of neuroscience has evolved toward recognizing the critical role of astroglia in shaping neuronal synaptic activity and along with the pre- and postsynapse is now considered an equal partner in tripartite synaptic transmission and plasticity. The relative youth of this recognition and a corresponding deficit in reagents and technologies for quantifying and manipulating astroglia relative to neurons continues to hamper advances in understanding tripartite synaptic physiology. Nonetheless, substantial advances have been made and are reviewed herein. We review the role of astroglia in synaptic function and regulation of behavior with an eye on how tripartite synapses figure into brain pathologies underlying behavioral impairments in psychiatric disorders, both from the perspective of measures in postmortem human brains and more subtle influences on tripartite synaptic regulation of behavior in animal models of psychiatric symptoms. Our goal is to provide the reader a well-referenced state-of-the-art understanding of current knowledge and predict what we may discover with deeper investigation of tripartite synapses using reagents and technologies not yet available.


Assuntos
Astrócitos , Transtornos Mentais , Animais , Humanos , Adolescente , Astrócitos/fisiologia , Transmissão Sináptica/fisiologia , Sinapses/fisiologia , Neurônios/fisiologia , Plasticidade Neuronal/fisiologia
7.
J Theor Biol ; 556: 111326, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36279957

RESUMO

The synaptic tagging and capture (STC) hypothesis not only explain the integration and association of synaptic activities, but also the formation of learning and memory. The synaptic pathways involved in the synaptic tagging and capture phenomenon are called STC pathways. The STC hypothesis provides a potential explanation of the neuronal and synaptic processes underlying the synaptic consolidation of memories. Several mechanisms and molecules have been proposed to explain the process of memory allocation and synaptic tags, respectively. However, a clear link between the STC hypothesis and memory allocation is still missing because the encoding of memories in neural circuits is mainly associated with strongly recurrently connected groups of neurons. To explore the mechanisms of potential synaptic tagging candidates and their involvement in the process of memory allocation, we develop a mathematical model for a single dendritic spine based on five essential criteria of a synaptic tag. By developing a mathematical model, we attempt to understand the roles of the potentially critical molecular networks underlying the STC and the essential attributes of a synaptic tag. We include essential memory molecules in the STC model that have been identified in earlier studies as crucial for STC pathways. CaMKII activation is critical for the setting of the initial tag; however, coordinated activities with other kinases and the biochemical pathways are necessary for the tag to be stable. PKA modulates NMDAR-mediated Ca2+ signalling. Similarly, PKA and ERK crosstalk is essential for Ca2+ - mediated protein synthesis during l-LTP. Our theoretical model explains the quantitative contribution of Tags and protein synthesis during l-LTP in synaptic strength.


Assuntos
Plasticidade Neuronal , Sinapses , Sinapses/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Modelos Teóricos , Potenciação de Longa Duração/fisiologia
8.
Neuropsychopharmacology ; 48(1): 54-60, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35995973

RESUMO

Neuronal and synaptic plasticity are widely used terms in the field of psychiatry. However, cellular neurophysiologists have identified two broad classes of plasticity. Hebbian forms of plasticity alter synaptic strength in a synapse specific manner in the same direction of the initial conditioning stimulation. In contrast, homeostatic plasticities act globally over longer time frames in a negative feedback manner to counter network level changes in activity or synaptic strength. Recent evidence suggests that homeostatic plasticity mechanisms can be rapidly engaged, particularly by fast-acting antidepressants such as ketamine to trigger behavioral effects. There is increasing evidence that several neuropsychoactive compounds either directly elicit changes in synaptic activity or indirectly tap into downstream signaling pathways to trigger homeostatic plasticity and subsequent behavioral effects. In this review, we discuss this recent work in the context of a wider paradigm where homeostatic synaptic plasticity mechanisms may provide novel targets for neuropsychiatric treatment advance.


Assuntos
Ketamina , Sinapses , Plasticidade Neuronal/fisiologia , Homeostase/fisiologia , Neurônios , Ketamina/farmacologia
9.
Neuropsychopharmacology ; 48(1): 121-144, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36038780

RESUMO

Synaptic plasticity configures interactions between neurons and is therefore likely to be a primary driver of behavioral learning and development. How this microscopic-macroscopic interaction occurs is poorly understood, as researchers frequently examine models within particular ranges of abstraction and scale. Computational neuroscience and machine learning models offer theoretically powerful analyses of plasticity in neural networks, but results are often siloed and only coarsely linked to biology. In this review, we examine connections between these areas, asking how network computations change as a function of diverse features of plasticity and vice versa. We review how plasticity can be controlled at synapses by calcium dynamics and neuromodulatory signals, the manifestation of these changes in networks, and their impacts in specialized circuits. We conclude that metaplasticity-defined broadly as the adaptive control of plasticity-forges connections across scales by governing what groups of synapses can and can't learn about, when, and to what ends. The metaplasticity we discuss acts by co-opting Hebbian mechanisms, shifting network properties, and routing activity within and across brain systems. Asking how these operations can go awry should also be useful for understanding pathology, which we address in the context of autism, schizophrenia and Parkinson's disease.


Assuntos
Plasticidade Neuronal , Sinapses , Plasticidade Neuronal/fisiologia , Sinapses/fisiologia , Neurônios , Redes Neurais de Computação , Cálcio , Modelos Neurológicos
10.
J Affect Disord ; 322: 63-75, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36372121

RESUMO

BACKGROUND: The mechanism by which synaptic plasticity mediates the occurrence of depression is unknown. Low-density lipoprotein receptor-related protein 1 (LRP1) affects axon growth and neurogenesis in the brain, but its role in depressive-like behaviors is poorly understood. METHODS: Adeno-associated virus-mediated small interfering RNA was injected into the bilateral hippocampus 14 days before chronic unpredicted mild stress (CUMS). Behavior performance was assessed for depressive-like behaviors. Western blot was conducted to detect levels of LRP1, neurogenesis-related proteins, synaptic markers, microtubule system molecules and Akt/GSK-3ß signaling-related proteins. Immunohistochemical staining was performed for LRP1 protein, immunofluorescence staining was conducted to determine the Sox2 protein, Nissl's staining and transmission electron microscope staining were used to observe hippocampal morphological features. RESULTS: The expression of hippocampal LRP1 was positively correlated with depressive-like behaviors. Treatment with iAAV-LRP1 exerted protective effects on depressive-like behaviors. LRP1 Knockdown relieved the inhibition of synaptic plasticity induced by CUMS. Expression of Sox2, GluR2 and SYP was significantly increased in iAAV-LRP1 CUMS rats. LRP1 knockdown reduced the p-tau (Ser262 and Thr404) and Acet-tubule levels in depressed rats. Finally, we found that LRP1 knockdown activated the PI3K/Akt pathway and inhibited GSK-3ß signal transduction. LIMITATIONS: More neurogenesis markers would be considered, and stereotactic injection into hippocampal DG region could be performed to investigate the effects of LRP1. CONCLUSIONS: These findings indicated that hippocampal LRP1 deficiency in stressed rats plays an important protective role in depressive-like behavior by increasing synaptic plasticity mediated by microtubule dynamic and activating Akt/GSK-3ß signaling pathway. Therefore, LRP1 may represent a potential therapeutic target for depression.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Ratos , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Hipocampo/metabolismo , Plasticidade Neuronal/fisiologia , Microtúbulos/metabolismo
11.
Glia ; 71(1): 36-43, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36408881

RESUMO

In the last decades, astrocytes have emerged as important regulatory cells actively involved in brain function by exchanging signaling with neurons. The endocannabinoid (eCB) signaling is widely present in many brain areas, being crucially involved in multiple brain functions and animal behaviors. The present review presents and discusses current evidence demonstrating that astrocytes sense eCBs released during neuronal activity and subsequently release gliotransmitters that regulate synaptic transmission and plasticity. The eCB signaling to astrocytes and the synaptic regulation mediated by astrocytes activated by eCBs are complex phenomena that exhibit exquisite spatial and temporal properties, a wide variety of downstream signaling mechanisms, and a large diversity of functional synaptic outcomes. Studies investigating this topic have revealed novel regulatory processes of synaptic function, like the lateral regulation of synaptic transmission and the active involvement of astrocytes in the spike-timing dependent plasticity, originally thought to be exclusively mediated by the coincident activity of pre- and postsynaptic neurons, following Hebbian rules for associative learning. Finally, the critical influence of astrocyte-mediated eCB signaling on animal behavior is also discussed.


Assuntos
Endocanabinoides , Plasticidade Neuronal , Animais , Plasticidade Neuronal/fisiologia , Transmissão Sináptica/fisiologia , Transdução de Sinais/fisiologia , Astrócitos/fisiologia
12.
PLoS Biol ; 20(11): e3001812, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36318572

RESUMO

Sleep is an essential process that consolidates memories by modulating synapses through poorly understood mechanisms. Here, we report that GABAergic synapses in hippocampal CA1 pyramidal neurons undergo daily rhythmic alterations. Specifically, wake inhibits phasic inhibition, whereas it promotes tonic inhibition compared to sleep. We further utilize a model of chemically induced inhibitory long-term potentiation (iLTP) to examine inhibitory plasticity. Intriguingly, while CA1 pyramidal neurons in both wake and sleep mice undergo iLTP, wake mice have a much higher magnitude. We also employ optogenetics and observe that inhibitory inputs from parvalbumin-, but not somatostatin-, expressing interneurons contribute to dynamic iLTP during sleep and wake. Finally, we demonstrate that synaptic insertion of α5-GABAA receptors underlies the wake-specific enhancement of iLTP at parvalbumin-synapses, which is independent of time of the day. These data reveal a previously unappreciated daily oscillation of inhibitory LTP in hippocampal neurons and uncover a dynamic contribution of inhibitory synapses in memory mechanisms across sleep and wake.


Assuntos
Hipocampo , Parvalbuminas , Animais , Camundongos , Hipocampo/fisiologia , Interneurônios/metabolismo , Plasticidade Neuronal/fisiologia , Parvalbuminas/metabolismo , Sono , Vigília
13.
Commun Biol ; 5(1): 1240, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376444

RESUMO

The cerebellar network is renowned for its regular architecture that has inspired foundational computational theories. However, the relationship between circuit structure, function and dynamics remains elusive. To tackle the issue, we developed an advanced computational modeling framework that allows us to reconstruct and simulate the structure and function of the mouse cerebellar cortex using morphologically realistic multi-compartmental neuron models. The cerebellar connectome is generated through appropriate connection rules, unifying a collection of scattered experimental data into a coherent construct and providing a new model-based ground-truth about circuit organization. Naturalistic background and sensory-burst stimulation are used for functional validation against recordings in vivo, monitoring the impact of cellular mechanisms on signal propagation, inhibitory control, and long-term synaptic plasticity. Our simulations show how mossy fibers entrain the local neuronal microcircuit, boosting the formation of columns of activity travelling from the granular to the molecular layer providing a new resource for the investigation of local microcircuit computation and of the neural correlates of behavior.


Assuntos
Córtex Cerebelar , Modelos Neurológicos , Camundongos , Animais , Córtex Cerebelar/fisiologia , Cerebelo/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia
14.
Cells ; 11(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36359749

RESUMO

The metabotropic glutamate (mGlu) receptor family consists of group I receptors (mGlu1 and mGlu5) that are positively coupled to phospholipase-C and group II (mGlu2 and mGlu3) and III receptors (mGlu4-8) that are negatively coupled to adenylyl cyclase. Of these, mGlu5 has emerged as a key factor in the induction and maintenance of persistent (>24 h) forms of hippocampal synaptic plasticity. Studies in freely behaving rodents have revealed that mGlu5 plays a pivotal role in the stabilisation of hippocampal long-term potentiation (LTP) and long-term depression (LTD) that are tightly associated with the acquisition and retention of knowledge about spatial experience. In this review article we shall address the state of the art in terms of the role of mGlu5 in forms of hippocampal synaptic plasticity related to experience-dependent information storage and present evidence that normal mGlu5 function is central to these processes.


Assuntos
Plasticidade Neuronal , Receptores de Glutamato Metabotrópico , Plasticidade Neuronal/fisiologia , Hipocampo/metabolismo , Potenciação de Longa Duração/fisiologia , Receptores de Glutamato Metabotrópico/metabolismo
15.
Trends Neurosci ; 45(12): 884-898, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36404455

RESUMO

Diverse inhibitory neurons in the mammalian brain shape circuit connectivity and dynamics through mechanisms of synaptic plasticity. Inhibitory plasticity can establish excitation/inhibition (E/I) balance, control neuronal firing, and affect local calcium concentration, hence regulating neuronal activity at the network, single neuron, and dendritic level. Computational models can synthesize multiple experimental results and provide insight into how inhibitory plasticity controls circuit dynamics and sculpts connectivity by identifying phenomenological learning rules amenable to mathematical analysis. We highlight recent studies on the role of inhibitory plasticity in modulating excitatory plasticity, forming structured networks underlying memory formation and recall, and implementing adaptive phenomena and novelty detection. We conclude with experimental and modeling progress on the role of interneuron-specific plasticity in circuit computation and context-dependent learning.


Assuntos
Plasticidade Neuronal , Neurônios , Humanos , Animais , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Aprendizagem/fisiologia , Mamíferos
16.
Sci Rep ; 12(1): 19631, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36385488

RESUMO

We analyze the effect of spike-timing-dependent plasticity (STDP) on a system of pulse-coupled class I neurons. Our research begins with a system of two mutually connected quadratic integrate-and-fire (QIF) neurons, which are canonical representatives of class I neurons. Along with various asymptotic modes previously observed in other neuronal models with plastic synapses, we found a stable synchronous mode characterized by unidirectional link from a slower neuron to a faster neuron. In this frequency-locked mode, the faster neuron emits multiple spikes per cycle of the slower neuron. We analytically obtain the Arnold tongues for this mode without STDP and with STDP. We also consider larger plastic networks of QIF neurons and show that the detected mode can manifest itself in such a way that slow neurons become pacemakers. As a result, slow and fast neurons can form large synchronous clusters that generate low-frequency oscillations. We demonstrate the generality of the results obtained with two connected QIF neurons using Wang-Buzsáki and Morris-Lecar biophysically plausible class I neuron models.


Assuntos
Modelos Neurológicos , Plasticidade Neuronal , Potenciais de Ação/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Sinapses/fisiologia
17.
Int J Mol Sci ; 23(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36361970

RESUMO

Visual system plasticity, the capability of visual connections to modify their structure and function in response to experience, is an essential property underlying the maturation of visual functions during development, behavioral flexibility in response to subtle environmental changes, and adaptive repair in conditions of disease or trauma [...].


Assuntos
Plasticidade Neuronal , Visão Ocular , Plasticidade Neuronal/fisiologia
18.
Int J Mol Sci ; 23(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36362131

RESUMO

Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged to be a predisposing or precipitating factor in neuropsychiatric diseases. There is a clear relationship between disturbances induced by stressful stimuli, especially long-lasting stimuli, and cognitive deficits in rodent models of affective disorders. Regular physical activity has a positive effect on the central nervous system (CNS) functions, contributes to an improvement in mood and of cognitive abilities (including memory and learning), and is correlated with an increase in the expression of the neurotrophic factors and markers of synaptic plasticity as well as a reduction in the inflammatory factors. Studies published so far show that the energy challenge caused by physical exercise can affect the CNS by improving cellular bioenergetics, stimulating the processes responsible for the removal of damaged organelles and molecules, and attenuating inflammation processes. Regular physical activity brings another important benefit: increased stress robustness. The evidence from animal studies is that a sedentary lifestyle is associated with stress vulnerability, whereas a physically active lifestyle is associated with stress resilience. Here, we have performed a comprehensive PubMed Search Strategy for accomplishing an exhaustive literature review. In this review, we discuss the findings from experimental studies on the molecular and neurobiological mechanisms underlying the impact of exercise on brain resilience. A thorough understanding of the mechanisms underlying the neuroprotective potential of preconditioning exercise and of the role of exercise in stress resilience, among other things, may open further options for prevention and therapy in the treatment of CNS diseases.


Assuntos
Encéfalo , Corrida , Animais , Encéfalo/fisiologia , Corrida/fisiologia , Plasticidade Neuronal/fisiologia , Cognição , Afeto , Estresse Psicológico/complicações
19.
Cells ; 11(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36429079

RESUMO

The AMPA glutamate receptor (AMPAR) is the major type of synaptic excitatory ionotropic receptor in the brain. AMPARs have four different subunits, GluA1-4 (each encoded by different genes, Gria1, Gria2, Gria3 and Gria4), that can form distinct tetrameric assemblies. The most abundant AMPAR subtypes in the hippocampus are GluA1/2 and GluA2/3 heterotetramers. Each subtype contributes differentially to mechanisms of synaptic plasticity, which may be in part caused by how these receptors are regulated by specific associated proteins. A broad range of AMPAR interacting proteins have been identified, including the well-studied transmembrane AMPA receptor regulatory proteins TARP-γ2 (also known as Stargazin) and TARP-γ8, Cornichon homolog 2 (CNIH-2) and many others. Several interactors were shown to affect biogenesis, AMPAR trafficking, and channel properties, alone or in distinct assemblies, and several revealed preferred binding to specific AMPAR subunits. To date, a systematic specific interactome analysis of the major GluA1/2 and GluA2/3 AMPAR subtypes separately is lacking. To reveal interactors belonging to specific AMPAR subcomplexes, we performed both expression and interaction proteomics on hippocampi of wildtype and Gria1- or Gria3 knock-out mice. Whereas GluA1/2 receptors co-purified TARP-γ8, synapse differentiation-induced protein 4 (SynDIG4, also known as Prrt1) and CNIH-2 with highest abundances, GluA2/3 receptors revealed strongest co-purification of CNIH-2, TARP-γ2, and Noelin1 (or Olfactomedin-1). Further analysis revealed that TARP-γ8-SynDIG4 interact directly and co-assemble into an AMPAR subcomplex especially at synaptic sites. Together, these data provide a framework for further functional analysis into AMPAR subtype specific pathways in health and disease.


Assuntos
Proteômica , Receptores de AMPA , Animais , Camundongos , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Sinapses/metabolismo , Plasticidade Neuronal/fisiologia , Hipocampo/metabolismo , Camundongos Knockout
20.
Proc Natl Acad Sci U S A ; 119(47): e2212004119, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36375086

RESUMO

Neural computational power is determined by neuroenergetics, but how and which energy substrates are allocated to various forms of memory engram is unclear. To solve this question, we asked whether neuronal fueling by glucose or lactate scales differently upon increasing neural computation and cognitive loads. Here, using electrophysiology, two-photon imaging, cognitive tasks, and mathematical modeling, we show that both glucose and lactate are involved in engram formation, with lactate supporting long-term synaptic plasticity evoked by high-stimulation load activity patterns and high attentional load in cognitive tasks and glucose being sufficient for less demanding neural computation and learning tasks. Indeed, we show that lactate is mandatory for demanding neural computation, such as theta-burst stimulation, while glucose is sufficient for lighter forms of activity-dependent long-term potentiation (LTP), such as spike timing-dependent plasticity (STDP). We find that subtle variations of spike number or frequency in STDP are sufficient to shift the on-demand fueling from glucose to lactate. Finally, we demonstrate that lactate is necessary for a cognitive task requiring high attentional load, such as the object-in-place task, and for the corresponding in vivo hippocampal LTP expression but is not needed for a less demanding task, such as a simple novel object recognition. Overall, these results demonstrate that glucose and lactate metabolism are differentially engaged in neuronal fueling depending on the complexity of the activity-dependent plasticity and behavior.


Assuntos
Glucose , Ácido Láctico , Potenciação de Longa Duração/fisiologia , Plasticidade Neuronal/fisiologia , Cognição
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...