Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27.934
Filtrar
1.
Nat Commun ; 12(1): 4839, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376673

RESUMO

The ability to maintain a sequence of items in memory is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human participants learned a fixed sequence of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining sequential order in memory.


Assuntos
Potenciais de Ação/fisiologia , Epilepsia/fisiopatologia , Aprendizagem/fisiologia , Neurônios/fisiologia , Ritmo Teta/fisiologia , Adolescente , Adulto , Epilepsia/diagnóstico , Feminino , Hipocampo/citologia , Hipocampo/fisiologia , Humanos , Masculino , Modelos Neurológicos , Neurônios/citologia , Estimulação Luminosa/métodos , Lobo Temporal/citologia , Lobo Temporal/fisiologia , Adulto Jovem
2.
Science ; 373(6552): 343-348, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34437154

RESUMO

Spatial memory in vertebrates requires brain regions homologous to the mammalian hippocampus. Between vertebrate clades, however, these regions are anatomically distinct and appear to produce different spatial patterns of neural activity. We asked whether hippocampal activity is fundamentally different even between distant vertebrates that share a strong dependence on spatial memory. We studied tufted titmice, food-caching birds capable of remembering many concealed food locations. We found mammalian-like neural activity in the titmouse hippocampus, including sharp-wave ripples and anatomically organized place cells. In a non-food-caching bird species, spatial firing was less informative and was exhibited by fewer neurons. These findings suggest that hippocampal circuit mechanisms are similar between birds and mammals, but that the resulting patterns of activity may vary quantitatively with species-specific ethological needs.


Assuntos
Tentilhões/fisiologia , Hipocampo/fisiologia , Neurônios/fisiologia , Passeriformes/fisiologia , Células de Lugar/fisiologia , Memória Espacial , Potenciais de Ação , Animais , Fenômenos Eletrofisiológicos , Comportamento Alimentar , Feminino , Tentilhões/anatomia & histologia , Hipocampo/anatomia & histologia , Hipocampo/citologia , Masculino , Vias Neurais , Passeriformes/anatomia & histologia , Sono
3.
Elife ; 102021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338632

RESUMO

Rapid progress in technologies such as calcium imaging and electrophysiology has seen a dramatic increase in the size and extent of neural recordings. Even so, interpretation of this data requires considerable knowledge about the nature of the representation and often depends on manual operations. Decoding provides a means to infer the information content of such recordings but typically requires highly processed data and prior knowledge of the encoding scheme. Here, we developed a deep-learning framework able to decode sensory and behavioral variables directly from wide-band neural data. The network requires little user input and generalizes across stimuli, behaviors, brain regions, and recording techniques. Once trained, it can be analyzed to determine elements of the neural code that are informative about a given variable. We validated this approach using electrophysiological and calcium-imaging data from rodent auditory cortex and hippocampus as well as human electrocorticography (ECoG) data. We show successful decoding of finger movement, auditory stimuli, and spatial behaviors - including a novel representation of head direction - from raw neural activity.


Assuntos
Estimulação Acústica , Córtex Auditivo/fisiologia , Aprendizado Profundo , Hipocampo/fisiologia , Movimento , Redes Neurais de Computação , Comportamento Espacial , Animais , Eletrocorticografia , Dedos , Humanos , Masculino , Camundongos , Ratos
4.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299127

RESUMO

Reelin is a secretory protein involved in a variety of processes in forebrain development and function, including neuronal migration, dendrite growth, spine formation, and synaptic plasticity. Most of the function of Reelin is focused on excitatory neurons; however, little is known about its effects on inhibitory neurons and inhibitory synapses. In this study, we investigated the phosphatidylinositol 3-kinase/Akt pathway of Reelin in primary cortical and hippocampal neurons. Individual neurons were visualized using immunofluorescence to distinguish inhibitory neurons from excitatory neurons. Reelin-rich protein supplementation significantly induced the phosphorylation of Akt and ribosomal S6 protein in excitatory neurons, but not in most inhibitory neurons. In somatostatin-expressing inhibitory neurons, one of major subtypes of inhibitory neurons, Reelin-rich protein supplementation induced the phosphorylation of S6. Subsequently, we investigated whether or not Reelin-rich protein supplementation affected dendrite development in cultured inhibitory neurons. Reelin-rich protein supplementation did not change the total length of dendrites in inhibitory neurons in vitro. Finally, we examined the development of inhibitory synapses in primary hippocampal neurons and found that Reelin-rich protein supplementation significantly reduced the density of gephyrin-VGAT-positive clusters in the dendritic regions without changing the expression levels of several inhibitory synapse-related proteins. These findings indicate a new role for Reelin in specific groups of inhibitory neurons and the development of inhibitory synapses, which may contribute to the underlying cellular mechanisms of RELN-associated neurological disorders.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Dendritos/fisiologia , Proteínas da Matriz Extracelular/metabolismo , Potenciais Pós-Sinápticos Inibidores , Proteínas do Tecido Nervoso/metabolismo , Inibição Neural , Plasticidade Neuronal , Neurônios/fisiologia , Serina Endopeptidases/metabolismo , Sinapses/fisiologia , Animais , Moléculas de Adesão Celular Neuronais/genética , Proteínas da Matriz Extracelular/genética , Hipocampo/citologia , Hipocampo/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Proteínas do Tecido Nervoso/genética , Neurogênese , Neurônios/citologia , Serina Endopeptidases/genética , Transdução de Sinais
5.
Toxicol Appl Pharmacol ; 426: 115641, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34242568

RESUMO

Bisphenol-A (BPA) is an environmental endocrine disruptor and impairs learning and memory. However, the direct evidence for BPA exposure affecting neural circuits has been limited. In this study, a virus tracing assay has been established to explore the brain's neural circuits. Thy1-Cre mice were used to investigate the effects of BPA on the neural projection of glutamatergic pyramidal neurons in hippocampal CA1 based on Thy1 promoter. These transgenic mice were orally exposed to BPA (0, 0.5 mg/kg/day) from postnatal day (PND) 0 to PND60 and then subjected to behavioral tests. Morris water maze(MWM)and Barnes maze's showed that the spatial memory was seriously impaired in BPA exposed Thy1-Cre mice. Virus tracing assay indicated that CA1 pyramidal neurons mainly received neural inputs from hippocampal CA3, entorhinal cortex (EC), and medial septum (MS). The analysis showed that BPA reduced the number of RV+ neurons in CA3 and EC but not MS. The immunohistochemistry experiment displayed that BPA decreased the percentage of CaMKIIRV+ cells in CA3 and EC. The results demonstrated that the synaptic connection of upstream glutamatergic neurons and CA1 pyramidal cells was weakened by BPA exposure. These point to potentially detrimental effects of BPA exposure on the excitatory neural circuit of CA3-CA1 and EC-CA1 in memory formation. Thus, our findings revealed that the decrease in excitatory neural circuits of CA3-CA1 and EC-CA1 contribute to the BPA-induced spatial memory deficits in Thy1-Cre mice.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Hipocampo/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Fenóis/toxicidade , Memória Espacial/efeitos dos fármacos , Animais , Feminino , Hipocampo/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Sinapses/efeitos dos fármacos
6.
Neuron ; 109(17): 2767-2780.e5, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34297916

RESUMO

Hippocampal ripples are prominent synchronization events generated by hippocampal neuronal assemblies. To date, ripples have been primarily associated with navigational memory in rodents and short-term episodic recollections in humans. Here, we uncover different profiles of ripple activity in the human hippocampus during the retrieval of recent and remote autobiographical events and semantic facts. We found that the ripple rate increased significantly before reported recall compared to control conditions. Patterns of ripple activity across multiple hippocampal sites demonstrated remarkable specificity for memory type. Intriguingly, these ripple patterns revealed a semantization dimension, in which patterns associated with autobiographical contents become similar to those of semantic memory as a function of memory age. Finally, widely distributed sites across the neocortex exhibited ripple-coupled activations during recollection, with the strongest activation found within the default mode network. Our results thus reveal a key role for hippocampal ripples in orchestrating hippocampal-cortical communication across large-scale networks involved in conscious recollection.


Assuntos
Ondas Encefálicas , Hipocampo/fisiologia , Memória Episódica , Adulto , Feminino , Humanos , Masculino , Rememoração Mental , Neocórtex/fisiologia , Semântica
7.
Int J Mol Sci ; 22(14)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34299282

RESUMO

Shrews are small animals found in many different habitats. Like other mammals, adult neurogenesis occurs in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus (DG) of the hippocampal formation. We asked whether the number of new generated cells in shrews depends on their brain size. We examined Crocidura russula and Neomys fodiens, weighing 10-22 g, and Crocidura olivieri and Suncus murinus that weigh three times more. We found that the density of proliferated cells in the SVZ was approximately at the same level in all species. These cells migrated from the SVZ through the rostral migratory stream to the olfactory bulb (OB). In this pathway, a low level of neurogenesis occurred in C. olivieri compared to three other species of shrews. In the DG, the rate of adult neurogenesis was regulated differently. Specifically, the lowest density of newly generated neurons was observed in C. russula, which had a substantial number of new neurons in the OB compared with C. olivieri. We suggest that the number of newly generated neurons in an adult shrew's brain is independent of the brain size, and molecular mechanisms of neurogenesis appeared to be different in two neurogenic structures.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Neurônios/fisiologia , Musaranhos/anatomia & histologia , Musaranhos/fisiologia , Animais , Peso Corporal , Movimento Celular/fisiologia , Proliferação de Células , Hipocampo/anatomia & histologia , Hipocampo/fisiologia , Ventrículos Laterais/anatomia & histologia , Ventrículos Laterais/fisiologia , Neurogênese , Bulbo Olfatório/anatomia & histologia , Bulbo Olfatório/fisiologia , Tamanho do Órgão
8.
Trends Cogn Sci ; 25(10): 831-842, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34281765

RESUMO

As we skillfully navigate through familiar places, neural computations of distances and coordinates escape our attention. However, we perceive clearly the division of space into socially meaningful territories. 'My space' versus 'your space' is a distinction familiar to all of us. Spatial frontiers are social in nature since they regulate individuals' access to utilities in space depending on hierarchy and affiliation. How does the brain integrate spatial geometry with social territory? We propose that the action of oxytocin (OT) in the entorhinal-hippocampal regions supports this process. Grounded on the functional role of the hypothalamic neuropeptide in the hippocampal system, we show how OT-induced plasticity may bias the geometrical coding of place and grid cells to represent social territories.


Assuntos
Hipocampo/fisiologia , Ocitocina/fisiologia , Encéfalo , Humanos
9.
Nat Rev Neurosci ; 22(8): 472-487, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34230644

RESUMO

An organism's survival can depend on its ability to recall and navigate to spatial locations associated with rewards, such as food or a home. Accumulating research has revealed that computations of reward and its prediction occur on multiple levels across a complex set of interacting brain regions, including those that support memory and navigation. However, how the brain coordinates the encoding, recall and use of reward information to guide navigation remains incompletely understood. In this Review, we propose that the brain's classical navigation centres - the hippocampus and the entorhinal cortex - are ideally suited to coordinate this larger network by representing both physical and mental space as a series of states. These states may be linked to reward via neuromodulatory inputs to the hippocampus-entorhinal cortex system. Hippocampal outputs can then broadcast sequences of states to the rest of the brain to store reward associations or to facilitate decision-making, potentially engaging additional value signals downstream. This proposal is supported by recent advances in both experimental and theoretical neuroscience. By discussing the neural systems traditionally tied to navigation and reward at their intersection, we aim to offer an integrated framework for understanding navigation to reward as a fundamental feature of many cognitive processes.


Assuntos
Córtex Entorrinal/fisiologia , Hipocampo/fisiologia , Recompensa , Memória Espacial/fisiologia , Navegação Espacial/fisiologia , Animais , Humanos , Vias Neurais/fisiologia
10.
Nat Commun ; 12(1): 3373, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099727

RESUMO

Theta rhythms temporally coordinate sequences of hippocampal place cell ensembles during active behaviors, while sharp wave-ripples coordinate place cell sequences during rest. We investigated whether such coordination of hippocampal place cell sequences is disrupted during error trials in a delayed match-to-place task. As a reward location was learned across trials, place cell sequences developed that represented temporally compressed paths to the reward location during the approach to the reward location. Less compressed paths were represented on error trials as an incorrect stop location was approached. During rest periods of correct but not error trials, place cell sequences developed a bias to replay representations of paths ending at the correct reward location. These results support the hypothesis that coordination of place cell sequences by theta rhythms and sharp wave-ripples develops as a reward location is learned and may be important for the successful performance of a spatial memory task.


Assuntos
Hipocampo/fisiologia , Células de Lugar/fisiologia , Desempenho Psicomotor/fisiologia , Memória Espacial/fisiologia , Ritmo Teta/fisiologia , Algoritmos , Animais , Teorema de Bayes , Hipocampo/citologia , Aprendizagem/fisiologia , Masculino , Ratos Long-Evans , Recompensa
11.
Science ; 372(6546): 1068-1073, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34083484

RESUMO

Mammalian medial and lateral hippocampal networks preferentially process spatial- and object-related information, respectively. However, the mechanisms underlying the assembly of such parallel networks during development remain largely unknown. Our study shows that, in mice, complementary expression of cell surface molecules teneurin-3 (Ten3) and latrophilin-2 (Lphn2) in the medial and lateral hippocampal networks, respectively, guides the precise assembly of CA1-to-subiculum connections in both networks. In the medial network, Ten3-expressing (Ten3+) CA1 axons are repelled by target-derived Lphn2, revealing that Lphn2- and Ten3-mediated heterophilic repulsion and Ten3-mediated homophilic attraction cooperate to control precise target selection of CA1 axons. In the lateral network, Lphn2-expressing (Lphn2+) CA1 axons are confined to Lphn2+ targets via repulsion from Ten3+ targets. Our findings demonstrate that assembly of parallel hippocampal networks follows a "Ten3→Ten3, Lphn2→Lphn2" rule instructed by reciprocal repulsions.


Assuntos
Orientação de Axônios , Axônios/fisiologia , Região CA1 Hipocampal/fisiologia , Hipocampo/fisiologia , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de Peptídeos/metabolismo , Animais , Região CA1 Hipocampal/citologia , Córtex Entorrinal/fisiologia , Feminino , Hipocampo/citologia , Ligantes , Masculino , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos , Proteínas do Tecido Nervoso/genética , Vias Neurais , Receptores de Peptídeos/genética , Transcriptoma
12.
Nature ; 595(7865): 80-84, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34135512

RESUMO

Hippocampal neurons encode physical variables1-7 such as space1 or auditory frequency6 in cognitive maps8. In addition, functional magnetic resonance imaging studies in humans have shown that the hippocampus can also encode more abstract, learned variables9-11. However, their integration into existing neural representations of physical variables12,13 is unknown. Here, using two-photon calcium imaging, we show that individual neurons in the dorsal hippocampus jointly encode accumulated evidence with spatial position in mice performing a decision-making task in virtual reality14-16. Nonlinear dimensionality reduction13 showed that population activity was well-described by approximately four to six latent variables, which suggests that neural activity is constrained to a low-dimensional manifold. Within this low-dimensional space, both physical and abstract variables were jointly mapped in an orderly manner, creating a geometric representation that we show is similar across mice. The existence of conjoined cognitive maps suggests that the hippocampus performs a general computation-the creation of task-specific low-dimensional manifolds that contain a geometric representation of learned knowledge.


Assuntos
Hipocampo/fisiologia , Conhecimento , Aprendizagem/fisiologia , Animais , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/fisiologia , Cálcio/metabolismo , Tomada de Decisões , Feminino , Hipocampo/citologia , Masculino , Camundongos , Modelos Neurológicos , Neurônios/metabolismo
13.
Nat Neurosci ; 24(8): 1065-1070, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34183867

RESUMO

Hippocampal theta rhythm is a therapeutic target because of its vital role in neuroplasticity, learning and memory. Curiously, theta differs across species. Here we show that theta rhythmicity is greatly amplified when rats run in virtual reality. A novel eta rhythm emerged in the CA1 cell layer, primarily in interneurons. Thus, multisensory experience governs hippocampal rhythms. Virtual reality can be used to boost or control brain rhythms and to alter neural dynamics, wiring and plasticity.


Assuntos
Ondas Encefálicas/fisiologia , Hipocampo/fisiologia , Realidade Virtual , Animais , Masculino , Ratos , Ratos Long-Evans
14.
J Alzheimers Dis ; 82(3): 1183-1202, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34151790

RESUMO

BACKGROUND: The use of Alzheimer's disease (AD) models obtained by intracerebral infusion of amyloid-ß (Aß) has been increasingly reported in recent years. Nonetheless, these models may present important challenges. OBJECTIVE: We have focused on canonical mechanisms of hippocampal-related neural plasticity to characterize a rat model obtained by an intracerebroventricular (icv) injection of soluble amyloid-ß42 (Aß42). METHODS: Animal behavior was evaluated in the elevated plus maze, Y-Maze spontaneous or forced alternation, Morris water maze, and open field, starting 2 weeks post-Aß42 infusion. Hippocampal neurogenesis was assessed 3 weeks after Aß42 injection. Aß deposition, tropomyosin receptor kinase B levels, and neuroinflammation were appraised at 3 and 14 days post-Aß42 administration. RESULTS: We found that immature neuronal dendritic morphology was abnormally enhanced, but proliferation and neuronal differentiation in the dentate gyrus was conserved one month after Aß42 injection. Surprisingly, animal behavior did not reveal changes in cognitive performance nor in locomotor and anxious-related activity. Brain-derived neurotrophic factor related-signaling was also unchanged at 3 and 14 days post-Aß icv injection. Likewise, astrocytic and microglial markers of neuroinflammation in the hippocampus were unaltered in these time points. CONCLUSION: Taken together, our data emphasize a high variability and lack of behavioral reproducibility associated with these Aß injection-based models, as well as the need for its further optimization, aiming at addressing the gap between preclinical AD models and the human disorder.


Assuntos
Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/toxicidade , Modelos Animais de Doenças , Hipocampo/fisiologia , Plasticidade Neuronal/fisiologia , Fragmentos de Peptídeos/toxicidade , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/administração & dosagem , Animais , Hipocampo/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Fragmentos de Peptídeos/administração & dosagem , Ratos , Ratos Wistar
15.
J Alzheimers Dis ; 82(3): 1015-1031, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34151792

RESUMO

BACKGROUND: Exercise training (ET) has neuroprotective effects in the hippocampus, a key brain region for memory that is vulnerable to age-related dysfunction. OBJECTIVE: We investigated the effects of ET on functional connectivity (FC) of the hippocampus in older adults with mild cognitive impairment (MCI) and a cognitively normal (CN) control group. We also assessed whether the ET-induced changes in hippocampal FC (Δhippocampal-FC) are associated with changes in memory task performance (Δmemory performance). METHODS: 32 older adults (77.0±7.6 years; 16 MCI and 16 CN) participated in the present study. Cardiorespiratory fitness tests, memory tasks (Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LM)), and resting-state fMRI were administered before and after a 12-week walking ET intervention. We utilized a seed-based correlation analysis using the bilateral anterior and posterior hippocampi as priori seed regions of interest. The associations of residualized ET-induced Δhippocampal-FC and Δmemory performance were assessed using linear regression. RESULTS: There were significant improvements in RAVLT Trial 1 and LM test performance after ET across participants. At baseline, MCI, compared to CN, demonstrated significantly lower posterior hippocampal FC. ET was associated with increased hippocampal FC across groups. Greater ET-related anterior and posterior hippocampal FC with right posterior cingulate were associated with improved LM recognition performance in MCI participants. CONCLUSION: Our findings indicate that hippocampal FC is significantly increased following 12-weeks of ET in older adults and, moreover, suggest that increased hippocampal FC may reflect neural network plasticity associated with ET-related improvements in memory performance in individuals diagnosed with MCI.


Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/terapia , Terapia por Exercício/métodos , Hipocampo/diagnóstico por imagem , Memória , Rede Nervosa/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/psicologia , Teste de Esforço/métodos , Teste de Esforço/psicologia , Teste de Esforço/tendências , Terapia por Exercício/psicologia , Terapia por Exercício/tendências , Feminino , Hipocampo/fisiologia , Humanos , Imageamento por Ressonância Magnética/tendências , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Caminhada/fisiologia , Caminhada/psicologia , Caminhada/tendências
16.
PLoS Biol ; 19(6): e3001275, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34077415

RESUMO

Episodic memory depends on interactions between the hippocampus and interconnected neocortical regions. Here, using data-driven analyses of resting-state functional magnetic resonance imaging (fMRI) data, we identified the networks that interact with the hippocampus-the default mode network (DMN) and a "medial temporal network" (MTN) that included regions in the medial temporal lobe (MTL) and precuneus. We observed that the MTN plays a critical role in connecting the visual network to the DMN and hippocampus. The DMN could be further divided into 3 subnetworks: a "posterior medial" (PM) subnetwork comprised of posterior cingulate and lateral parietal cortices; an "anterior temporal" (AT) subnetwork comprised of regions in the temporopolar and dorsomedial prefrontal cortex; and a "medial prefrontal" (MP) subnetwork comprised of regions primarily in the medial prefrontal cortex (mPFC). These networks vary in their functional connectivity (FC) along the hippocampal long axis and represent different kinds of information during memory-guided decision-making. Finally, a Neurosynth meta-analysis of fMRI studies suggests new hypotheses regarding the functions of the MTN and DMN subnetworks, providing a framework to guide future research on the neural architecture of episodic memory.


Assuntos
Hipocampo/fisiologia , Rede Nervosa/fisiologia , Humanos , Memória/fisiologia , Descanso/fisiologia , Análise e Desempenho de Tarefas , Lobo Temporal/fisiologia , Vias Visuais/fisiologia
17.
PLoS Comput Biol ; 17(6): e1008927, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34061837

RESUMO

Information processing can leave distinct footprints on the statistics of neural spiking. For example, efficient coding minimizes the statistical dependencies on the spiking history, while temporal integration of information may require the maintenance of information over different timescales. To investigate these footprints, we developed a novel approach to quantify history dependence within the spiking of a single neuron, using the mutual information between the entire past and current spiking. This measure captures how much past information is necessary to predict current spiking. In contrast, classical time-lagged measures of temporal dependence like the autocorrelation capture how long-potentially redundant-past information can still be read out. Strikingly, we find for model neurons that our method disentangles the strength and timescale of history dependence, whereas the two are mixed in classical approaches. When applying the method to experimental data, which are necessarily of limited size, a reliable estimation of mutual information is only possible for a coarse temporal binning of past spiking, a so-called past embedding. To still account for the vastly different spiking statistics and potentially long history dependence of living neurons, we developed an embedding-optimization approach that does not only vary the number and size, but also an exponential stretching of past bins. For extra-cellular spike recordings, we found that the strength and timescale of history dependence indeed can vary independently across experimental preparations. While hippocampus indicated strong and long history dependence, in visual cortex it was weak and short, while in vitro the history dependence was strong but short. This work enables an information-theoretic characterization of history dependence in recorded spike trains, which captures a footprint of information processing that is beyond time-lagged measures of temporal dependence. To facilitate the application of the method, we provide practical guidelines and a toolbox.


Assuntos
Potenciais de Ação/fisiologia , Hipocampo/fisiologia , Córtex Visual/fisiologia , Simulação por Computador , Hipocampo/citologia , Humanos , Modelos Neurológicos , Neurônios/fisiologia , Córtex Visual/citologia
18.
Nat Commun ; 12(1): 3558, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117238

RESUMO

Hippocampal place cells contribute to mammalian spatial navigation and memory formation. Numerous models have been proposed to explain the location-specific firing of this cognitive representation, but the pattern of excitatory synaptic input leading to place firing is unknown, leaving no synaptic-scale explanation of place coding. Here we used resonant scanning two-photon microscopy to establish the pattern of synaptic glutamate input received by CA1 place cells in behaving mice. During traversals of the somatic place field, we found increased excitatory dendritic input, mainly arising from inputs with spatial tuning overlapping the somatic field, and functional clustering of this input along the dendrites over ~10 µm. These results implicate increases in total excitatory input and co-activation of anatomically clustered synaptic input in place firing. Since they largely inherit their fields from upstream synaptic partners with similar fields, many CA1 place cells appear to be part of multi-brain-region cell assemblies forming representations of specific locations.


Assuntos
Hipocampo/fisiologia , Células de Lugar/fisiologia , Memória Espacial/fisiologia , Sinapses/fisiologia , Potenciais de Ação/fisiologia , Animais , Comportamento Animal , Região CA1 Hipocampal , Dendritos/fisiologia , Ácido Glutâmico , Hipocampo/diagnóstico por imagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Neurológicos , Plasticidade Neuronal/fisiologia , Neurotransmissores
19.
Psychopharmacology (Berl) ; 238(8): 2297-2312, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33991198

RESUMO

RATIONALE AND OBJECTIVE: Environmental enrichment (EE) has been shown in old rats to improve learning and memory. Vitamin D (VitD) has also been shown to modulate age-related, cognitive dysfunction. As both EE and VitD could work to improve cognition via enhancement of neurotrophic factors, their effects might occlude one another. Therefore, a clinically relevant question is whether noted cognition-promoting effects of EE and VitD can co-occur. METHODS: Aged rats were housed for 6 weeks in one of three housing conditions: environmentally enriched (EE), socially enriched (SE), or standard condition (SC). Further, a 4th group was co-treated with VitD supplementation (400 IU kg-1 daily, 6 weeks) under EE conditions (EE + VitD). RESULTS: Treatment with VitD and EE housing were associated with higher score on measures of learning and memory and exhibited lower anxiety scores compared to EE alone, SE or SC as assayed in the elevated plus maze, Morris water maze, passive avoidance, and open field tasks. Additionally, in the EE + VitD group, mRNA expression levels of NGF, TrkA, BDNF, Nrf2, and IGF-1 were significantly higher compared to expression seen in the EE group. Furthermore, field potential recordings showed that EE + VitD resulted in a greater enhancement of hippocampal LTP and neuronal excitability when compared to EE alone. CONCLUSIONS: These findings demonstrate that in aged rats exposure to EE and VitD results in effects on hippocampal cognitive dysfunction and molecular mechanisms which are greater than effects of EE alone, suggesting potential for synergistic therapeutic effects for management of age-related cognitive decline.


Assuntos
Envelhecimento/fisiologia , Meio Ambiente , Memória/fisiologia , Plasticidade Neuronal/fisiologia , Aprendizagem Espacial/fisiologia , Vitamina D/administração & dosagem , Envelhecimento/efeitos dos fármacos , Envelhecimento/psicologia , Animais , Cognição/efeitos dos fármacos , Cognição/fisiologia , Suplementos Nutricionais , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Aprendizagem Espacial/efeitos dos fármacos
20.
Nat Protoc ; 16(6): 2947-2967, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33990799

RESUMO

Rigorous investigation of synaptic transmission requires analysis of unitary synaptic events by simultaneous recording from presynaptic terminals and postsynaptic target neurons. However, this has been achieved at only a limited number of model synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical presynaptic terminals have been largely inaccessible to direct presynaptic recording, due to their small size. Here, we describe a protocol for improved subcellular patch-clamp recording in rat and mouse brain slices, with the synapse in a largely intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals are stimulated minimally invasively in the bouton-attached configuration, in which the cytoplasmic content remains unperturbed, or in the whole-bouton configuration, in which the cytoplasmic composition can be precisely controlled. Paired pre-postsynaptic recordings can be integrated with biocytin labeling and morphological analysis, allowing correlative investigation of synapse structure and function. Paired recordings can be obtained from mossy fiber terminals in slices from both rats and mice, implying applicability to genetically modified synapses. Paired recordings can also be performed together with axon tract stimulation or optogenetic activation, allowing comparison of unitary and compound synaptic events in the same target cell. Finally, paired recordings can be combined with spontaneous event analysis, permitting collection of miniature events generated at a single identified synapse. In conclusion, the subcellular patch-clamp techniques detailed here should facilitate analysis of biophysics, plasticity and circuit function of cortical synapses in the mammalian central nervous system.


Assuntos
Hipocampo/fisiologia , Técnicas de Patch-Clamp/métodos , Terminações Pré-Sinápticas/fisiologia , Animais , Camundongos , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...