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1.
J Neurosci Res ; 101(1): 48-69, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36128957

RESUMO

Memory labilization, the process by which memories become susceptible to update, is essential for memory reconsolidation and has been a target for novel therapies for traumatic memory-associated disorders. Maternal separation (MS) in male rats produced memories resistant to labilization in adulthood. Based on previous results, we hypothesized that temporal desynchronization between the dorsal hippocampus (DHc) and the basolateral amygdala (BLA), during memory retrieval, could be responsible for this impairment. Our goal was to investigate possible differences in oscillatory activity and synchrony between the DHc and BLA during fear memory reactivation, between MS and non-handled (NH) rats. We used male adult Wistar rats, NH or MS, with electrodes for local field potential (LFP) recordings implanted in the DHc and BLA. Animals were submitted to aversive memory reactivation by exposure to the conditioned context (Reat) or to pseudo-reactivation in a neutral context (pReat), and LFP was recorded. Plasticity markers linked to reconsolidation were evaluated one hour after reactivation. The power of delta oscillations and DHc-BLA synchrony in Reat animals was increased, during freezing. Besides, delta modulation of gamma oscillations amplitude in the BLA was associated with the increase in DHc Zif268 levels, an immediate early gene specifically associated with reconsolidation. Concerning early life stress, we found lower power of delta and strength of delta-gamma oscillations coupling in MS rats, compared to NH, which could explain the low Zif268 levels in a subgroup of MS animals. These results suggest a role for delta oscillations in memory reactivation that should be further investigated.


Assuntos
Tonsila do Cerebelo , Privação Materna , Animais , Masculino , Ratos , Ratos Wistar , Tonsila do Cerebelo/fisiologia , Memória/fisiologia , Hipocampo/fisiologia
2.
Cell Rep ; 41(8): 111700, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36417882

RESUMO

Decades of work propose that hippocampal activity supports internal representation of learned experiences and contexts, allowing individuals to form long-term memories and quickly adapt behavior to changing environments. However, recent studies insinuate hippocampal representations can drift over time, raising the question: how could the hippocampus hold stable memories when activity of its neuronal maps fluctuates? We hypothesized that task-dependent hippocampal maps set by learning rules and structured attention stabilize as a function of behavioral performance. To test this, we imaged hippocampal CA1 pyramidal neurons during learning and memory recall phases of a new task where mice use odor cues to navigate between two reward zones. Across learning, both orthogonal and overlapping task-dependent place maps form rapidly, discriminating trial context with strong correlation to behavioral performance. Once formed, task-selective place maps show increased long-term stability during memory recall phases. We conclude that memory demand and attention stabilize hippocampal activity to maintain contextually rich spatial representations.


Assuntos
Células de Lugar , Camundongos , Animais , Memória/fisiologia , Aprendizagem/fisiologia , Hipocampo/fisiologia , Células Piramidais/fisiologia
3.
J Neurosci ; 42(41): 7690-7706, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36414011

RESUMO

Persistent firing is commonly reported in both cortical and subcortical neurons under a variety of behavioral conditions. Yet the mechanisms responsible for persistent activity are only partially resolved with support for both intrinsic and synaptic circuit-based mechanisms. Little also is known about physiological factors that enable epochs of persistent firing to continue beyond brief pauses and then spontaneously terminate. In the present study, we used intracellular recordings in rat (both sexes) neocortical and hippocampal brain slices to assess the ionic mechanisms underlying persistent firing dynamics. Previously, we showed that blockade of ether-á-go-go-related gene (ERG) potassium channels abolished intrinsic persistent firing in the presence of low concentrations of muscarinic receptor agonists and following optogenetic activation of cholinergic axons. Here we show the slow dynamics of ERG conductance changes allows persistent firing to outlast the triggering stimulus and even to initiate discharges following ∼7 s poststimulus firing pauses. We find that persistent firing dynamics is regulated by the interaction between ERG conductance and spike afterhyperpolarizations (AHPs). Increasing the amplitude of spike AHPs using either SK channel activators or a closed-loop reactive feedback system allows persistent discharges to spontaneously terminate in both neocortical neurons and hippocampal CA1 pyramidal cells. The interplay between ERG and the potassium channels that mediate spike AHPs grades the duration of persistent firing, providing a novel, generalizable mechanism to explain self-terminating persistent firing modes observed behaving animals.SIGNIFICANCE STATEMENT Many classes of neurons generate prolonged spiking responses to transient stimuli. These discharges often outlast the stimulus by seconds to minutes in some in vitro models of persistent firing. While recent work has identified key synaptic and intrinsic components that enable persistent spiking responses, less is known about mechanisms that can terminate and regulate the dynamics of these responses. The present study identified the spike afterhyperpolarizations as a potent mechanism that regulates the duration of persistent firing. We found that amplifying spike afterpotentials converted bistable persistent firing into self-terminating discharges. Varying the spike AHP amplitude grades the duration of persistent discharges, generating in vitro responses that mimic firing modes associated with neurons associated with short-term memory function.


Assuntos
Neocórtex , Masculino , Feminino , Ratos , Animais , Potenciais de Ação/fisiologia , Células Piramidais/fisiologia , Hipocampo/fisiologia , Canais de Potássio
4.
Mol Brain ; 15(1): 92, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411441

RESUMO

The development, maturation, and plasticity of neural circuits are strongly influenced by experience and the interaction of an individual with their environment can have a long-lasting effect on cognitive function. Using an enriched environment (EE) paradigm, we have recently demonstrated that enhancing social, physical, and sensory activity during the pre-weaning time in mice led to an increase of inhibitory and excitatory synapses in the dentate gyrus (DG) of the hippocampus. The structural plasticity induced by experience may affect information processing in the circuit. The DG performs pattern separation, a computation that enables the encoding of very similar and overlapping inputs into dissimilar outputs. In the presented study, we have tested the hypothesis that an EE in juvenile mice will affect DG's functions that are relevant for pattern separation: the decorrelation of the inputs from the entorhinal cortex (EC) and the recruitment of the principal excitatory granule cell (GC) during behavior. First, using a novel slice electrophysiology protocol, we found that the transformation of the incoming signal from the EC afferents by individual GC is moderately affected by EE. We further show that EE does not affect behaviorally induced recruitment of principal excitatory GC. Lastly, using the novel object recognition task, a hippocampus-dependent memory test, we show that the ontogeny of this discrimination task was similar among the EE mice and the controls. Taken together, our work demonstrates that pre-weaning enrichment moderately affects DG function.


Assuntos
Giro Denteado , Hipocampo , Animais , Camundongos , Giro Denteado/fisiologia , Hipocampo/fisiologia , Córtex Entorrinal , Neurônios/fisiologia , Sinapses
5.
Cell Rep ; 41(7): 111643, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36384113

RESUMO

Episodic memories formed in early childhood rapidly decay, but their latent traces remain stored long term. These memories require the dorsal hippocampus (dHPC) and seem to undergo a developmental critical period. It remains to be determined whether the maturation of parvalbumin interneurons (PVIs), a major mechanism of critical periods, contributes to memory development. Here, we show that episodic infantile learning significantly increases the levels of parvalbumin in the dHPC 48 h after training. Chemogenetic inhibition of PVIs before learning indicated that these neurons are required for infantile memory formation. A bilateral dHPC injection of the γ-aminobutyric acid type A receptor agonist diazepam after training elicited long-term memory expression in infant rats, although direct PVI chemogenetic activation had no effect. Finally, PVI activity was required for brain-derived neurotrophic factor (BDNF)-dependent maturation of memory competence, i.e., adult-like long-term memory expression. Thus, dHPC PVIs are critical for the formation of infantile memories and for memory development.


Assuntos
Memória Episódica , Parvalbuminas , Pré-Escolar , Ratos , Humanos , Animais , Interneurônios/fisiologia , Hipocampo/fisiologia
6.
Artigo em Russo | MEDLINE | ID: mdl-36385089

RESUMO

The article presents scientific evidence that new neurons from progenitor cells throughout life in almost all animals with a nervous system are an integral component of neuronal ontogenesis and plasticity.It has been shown that there are neural stem cells in the brain that give rise to adult neurogenesis, occurring primarily in the dentate gyrus, a subregion of the hippocampus important for learning, memory, and emotion. With age, there is a decrease in adult neurogenesis, which is associated with a decrease in cognitive functions. Newly formed neurons and «immature¼ neurons together constitute a potential reservoir of young cells («brain reserve¼) that can be used to prevent aging and/or delay the onset/reduce the impact of neurological disorders.The possibility of using neurogenic processes for therapeutic purposes to reduce pain and improve the quality of life of patients is implied.


Assuntos
Células-Tronco Neurais , Qualidade de Vida , Animais , Neurogênese/fisiologia , Hipocampo/fisiologia , Neurônios/fisiologia
7.
Elife ; 112022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36394367

RESUMO

Competition between overlapping memories is considered one of the major causes of forgetting, and it is still unknown how the human brain resolves such mnemonic conflict. In the present magnetoencephalography (MEG) study, we empirically tested a computational model that leverages an oscillating inhibition algorithm to minimise overlap between memories. We used a proactive interference task, where a reminder word could be associated with either a single image (non-competitive condition) or two competing images, and participants were asked to always recall the most recently learned word-image association. Time-resolved pattern classifiers were trained to detect the reactivated content of target and competitor memories from MEG sensor patterns, and the timing of these neural reactivations was analysed relative to the phase of the dominant hippocampal 3 Hz theta oscillation. In line with our pre-registered hypotheses, target and competitor reactivations locked to different phases of the hippocampal theta rhythm after several repeated recalls. Participants who behaviourally experienced lower levels of interference also showed larger phase separation between the two overlapping memories. The findings provide evidence that the temporal segregation of memories, orchestrated by slow oscillations, plays a functional role in resolving mnemonic competition by separating and prioritising relevant memories under conditions of high interference.


Assuntos
Hipocampo , Ritmo Teta , Humanos , Ritmo Teta/fisiologia , Hipocampo/fisiologia , Rememoração Mental/fisiologia , Memória/fisiologia , Inibição Psicológica
8.
J Neurosci ; 42(45): 8450-8459, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36351831

RESUMO

Since the discovery of conspicuously spatially tuned neurons in the hippocampal formation over 50 years ago, characterizing which, where, and how neurons encode navigationally relevant variables has been a major thrust of navigational neuroscience. While much of this effort has centered on the hippocampal formation and functionally-adjacent structures, recent work suggests that spatial codes, in some form or another, can be found throughout the brain, even in areas traditionally associated with sensation, movement, and executive function. In this review, we highlight these unexpected results, draw insights from comparison of these codes across contexts, regions, and species, and finally suggest an avenue for future work to make sense of these diverse and dynamic navigational codes.


Assuntos
Navegação Espacial , Navegação Espacial/fisiologia , Encéfalo/fisiologia , Mapeamento Encefálico , Hipocampo/fisiologia , Neurônios/fisiologia
9.
Nat Commun ; 13(1): 6721, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344498

RESUMO

The environmental context associated with previous drug consumption is a potent trigger for drug relapse. However, the mechanism by which neural representations of context are modified to incorporate information associated with drugs of abuse remains unknown. Using longitudinal calcium imaging in freely behaving mice, we find that unlike the associative learning of natural reward, drug-context associations for psychostimulants and opioids are encoded in a specific subset of hippocampal neurons. After drug conditioning, these neurons weakened their spatial coding for the non-drug paired context, resulting in an orthogonal representation for the drug versus non-drug context that was predictive of drug-seeking behavior. Furthermore, these neurons were selected based on drug-spatial experience and were exclusively tuned to animals' allocentric position. Together, this work reveals how drugs of abuse alter the hippocampal circuit to encode drug-context associations and points to the possibility of targeting drug-associated memory in the hippocampus.


Assuntos
Condicionamento Clássico , Hipocampo , Camundongos , Animais , Hipocampo/fisiologia , Neurônios/fisiologia , Recompensa , Comportamento de Procura de Droga
10.
Nat Commun ; 13(1): 6729, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344524

RESUMO

The hippocampus has been a focus of memory research since H.M's surgery abolished his ability to form new memories, yet its mechanistic role in memory remains debated. Here, we identify a candidate memory mechanism: an anticipatory hippocampal "convergence state", observed while awaiting valuable information, and which predicts subsequent learning. During fMRI, participants viewed trivia questions eliciting high or low curiosity, followed seconds later by its answer. We reasoned that encoding success requires a confluence of conditions, so that hippocampal states more conducive to memory formation should converge in state space. To operationalize convergence of neural states, we quantified the typicality of multivoxel patterns in the medial temporal lobes during anticipation and encoding of trivia answers. We found that the typicality of anticipatory hippocampal patterns increased during high curiosity. Crucially, anticipatory hippocampal pattern typicality increased with dopaminergic midbrain activation and uniquely accounted for the association between midbrain activation and subsequent recall. We propose that hippocampal convergence states may complete a cascade from motivation and midbrain activation to memory enhancement, and may be a general predictor of memory formation.


Assuntos
Hipocampo , Mesencéfalo , Humanos , Hipocampo/fisiologia , Mesencéfalo/fisiologia , Aprendizagem/fisiologia , Lobo Temporal/fisiologia , Rememoração Mental , Imageamento por Ressonância Magnética
11.
Nat Commun ; 13(1): 6715, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344570

RESUMO

Neuronal plasticity has been shown to be causally linked to coincidence detection through dendritic spikes (dSpikes). We demonstrate the existence of SPW-R-associated, branch-specific, local dSpikes and their computational role in basal dendrites of hippocampal PV+ interneurons in awake animals. To measure the entire dendritic arbor of long thin dendrites during SPW-Rs, we used fast 3D acousto-optical imaging through an eccentric deep-brain adapter and ipsilateral local field potential recording. The regenerative calcium spike started at variable, NMDA-AMPA-dependent, hot spots and propagated in both direction with a high amplitude beyond a critical distance threshold (~150 µm) involving voltage-gated calcium channels. A supralinear dendritic summation emerged during SPW-R doublets when two successive SPW-R events coincide within a short temporal window (~150 ms), e.g., during more complex association tasks, and generated large dSpikes with an about 2.5-3-fold amplitude increase which propagated down to the soma. Our results suggest that these doublet-associated dSpikes can work as a dendritic-level temporal and spatial coincidence detector during SPW-R-related network computation in awake mice.


Assuntos
Interneurônios , Parvalbuminas , Camundongos , Animais , Potenciais de Ação/fisiologia , Interneurônios/fisiologia , Dendritos/fisiologia , Neurônios/fisiologia , Hipocampo/fisiologia , Células Piramidais/fisiologia
12.
Elife ; 112022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36346218

RESUMO

Efficient planning in complex environments requires that uncertainty associated with current inferences and possible consequences of forthcoming actions is represented. Representation of uncertainty has been established in sensory systems during simple perceptual decision making tasks but it remains unclear if complex cognitive computations such as planning and navigation are also supported by probabilistic neural representations. Here, we capitalized on gradually changing uncertainty along planned motion trajectories during hippocampal theta sequences to capture signatures of uncertainty representation in population responses. In contrast with prominent theories, we found no evidence of encoding parameters of probability distributions in the momentary population activity recorded in an open-field navigation task in rats. Instead, uncertainty was encoded sequentially by sampling motion trajectories randomly and efficiently in subsequent theta cycles from the distribution of potential trajectories. Our analysis is the first to demonstrate that the hippocampus is well equipped to contribute to optimal planning by representing uncertainty.


Assuntos
Hipocampo , Ritmo Teta , Ratos , Animais , Hipocampo/fisiologia , Incerteza , Probabilidade , Ritmo Teta/fisiologia
13.
BMC Biol ; 20(1): 250, 2022 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-36352395

RESUMO

BACKGROUND: Schema, a concept from cognitive psychology used to explain how new information is integrated with previous experience, is a framework of acquired knowledge within associative network structures as biological correlate, which allows new relevant information to be quickly assimilated by parallel cortical encoding in the hippocampus (HPC) and cortex. Previous work demonstrated that myelin generation in the anterior cingulate cortex (ACC) plays a critical role for dynamic paired association (PA) learning and consolidation, while astrocytes in ACC play a vital role in cognitive decision-making. However, circuit components and mechanism involving HPC-anterior cingulate cortex (ACC) during schema formation remain uncertain. Moreover, the correlation between HPC-ACC circuit and HPC astrocytic activity is unclear. RESULTS: Utilizing a paired association (PA) behavioral paradigm, we dynamically recorded calcium signals of CA1-ACC projection neurons and ACC neurons during schema formation. Depending on the characteristics of the calcium signals, three distinct stages of schema establishment process were identified. The recruitment of CA1-ACC network was investigated in each stage under CA1 astrocytes Gi pathway chemogenetic activation. Results showed that CA1-ACC projecting neurons excitation gradually decreased along with schema development, while ACC neurons revealed an excitation peak in the middle stage. CA1 astrocytic Gi pathway activation will disrupt memory schema development by reducing CA1-ACC projection neuron recruitment in the initial stage and prevent both CA1-ACC projection neurons and ACC neuron excitation in the middle stage. CA1 astrocytes Gi markedly suppress new PA assimilation into the established memory schema. CONCLUSIONS: These results not only reveal the dynamic feature of CA1-ACC network during schema establishment, but also suggest CA1 astrocyte contribution in different stages of schema establishment.


Assuntos
Astrócitos , Cálcio , Astrócitos/metabolismo , Cálcio/metabolismo , Hipocampo/fisiologia , Giro do Cíngulo/metabolismo , Neurônios/fisiologia
14.
PLoS One ; 17(11): e0277414, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36374865

RESUMO

The mammalian hippocampus (Hp) can be functionally segregated along its septotemporal axis, with involvement of dorsal hippocampus (dHp) in spatial memory and ventral hippocampus (vHp) in stress responses and emotional behaviour. In the present study, we investigate comparable functional segregation in proposed homologues within the avian brain. Using Japanese quail (Coturnix Japonica), we report that bilateral lesions of the rostral hippocampus (rHp) produce robust deficits in a spatial Y-maze discrimination (YMD) test while sparing performance during contextual fear conditioning (CFC), comparable to results from lesions to homologous regions in mammals. In contrast, caudal hippocampus (cHp) lesions failed to produce deficits in either CFC or YMD, suggesting that, unlike mammals, both cHp and rHp of birds can support emotional behavior. These observations demonstrate functional segregation along the rostrocaudal axis of the avian Hp that is comparable in part to distinctions seen along the mammalian hippocampal septotemporal axis.


Assuntos
Coturnix , Hipocampo , Animais , Coturnix/fisiologia , Hipocampo/fisiologia , Aprendizagem em Labirinto/fisiologia , Memória Espacial , Medo , Mamíferos
15.
Cells ; 11(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36428984

RESUMO

Metabotropic glutamate 5 receptors (mGlu5) are thought to play an important role in mediating emotional information processing. In particular, negative allosteric modulators (NAMs) of mGlu5 have received a lot of attention as potential novel treatments for several neuropsychiatric diseases, including anxiety-related disorders. The aim of this study was to assess the influence of pre- and post-training mGlu5 inactivation in cued fear conditioned mice on neuronal oscillatory activity during fear retrieval. For this study we used the recently developed mGlu5 NAM Alloswicth-1 administered systemically. Injection of Alloswicth-1 before, but not after, fear conditioning resulted in a significant decrease in freezing upon fear retrieval. Mice injected with Alloswicth-1 pre-training were also implanted with recording microelectrodes into both the medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC). The recordings revealed a reduction in theta rhythmic activity (4-12 Hz) in both the mPFC and vHPC during fear retrieval. These results indicate that inhibition of mGlu5 signaling alters local oscillatory activity in principal components of the fear brain network underlying a reduced response to a predicted threat.


Assuntos
Medo , Córtex Pré-Frontal , Camundongos , Animais , Córtex Pré-Frontal/metabolismo , Medo/fisiologia , Hipocampo/fisiologia
16.
Proc Natl Acad Sci U S A ; 119(45): e2206704119, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36322739

RESUMO

New neurons are continuously generated in the subgranular zone of the dentate gyrus throughout adulthood. These new neurons gradually integrate into hippocampal circuits, forming new naive synapses. Viewed from this perspective, these new neurons may represent a significant source of "wiring" noise in hippocampal networks. In machine learning, such noise injection is commonly used as a regularization technique. Regularization techniques help prevent overfitting training data and allow models to generalize learning to new, unseen data. Using a computational modeling approach, here we ask whether a neurogenesis-like process similarly acts as a regularizer, facilitating generalization in a category learning task. In a convolutional neural network (CNN) trained on the CIFAR-10 object recognition dataset, we modeled neurogenesis as a replacement/turnover mechanism, where weights for a randomly chosen small subset of hidden layer neurons were reinitialized to new values as the model learned to categorize 10 different classes of objects. We found that neurogenesis enhanced generalization on unseen test data compared to networks with no neurogenesis. Moreover, neurogenic networks either outperformed or performed similarly to networks with conventional noise injection (i.e., dropout, weight decay, and neural noise). These results suggest that neurogenesis can enhance generalization in hippocampal learning through noise injection, expanding on the roles that neurogenesis may have in cognition.


Assuntos
Memória , Neurogênese , Memória/fisiologia , Neurogênese/fisiologia , Hipocampo/fisiologia , Neurônios/fisiologia , Sinapses , Giro Denteado/fisiologia
17.
Science ; 378(6619): eabm8797, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36378956

RESUMO

Genetically encoded fluorescent voltage indicators are ideally suited to reveal the millisecond-scale interactions among and between targeted cell populations. However, current indicators lack the requisite sensitivity for in vivo multipopulation imaging. We describe next-generation green and red voltage sensors, Ace-mNeon2 and VARNAM2, and their reverse response-polarity variants pAce and pAceR. Our indicators enable 0.4- to 1-kilohertz voltage recordings from >50 spiking neurons per field of view in awake mice and ~30-minute continuous imaging in flies. Using dual-polarity multiplexed imaging, we uncovered brain state-dependent antagonism between neocortical somatostatin-expressing (SST+) and vasoactive intestinal peptide-expressing (VIP+) interneurons and contributions to hippocampal field potentials from cell ensembles with distinct axonal projections. By combining three mutually compatible indicators, we performed simultaneous triple-population imaging. These approaches will empower investigations of the dynamic interplay between neuronal subclasses at single-spike resolution.


Assuntos
Potenciais de Ação , Hipocampo , Imagem Molecular , Neurônios , Córtex Visual , Animais , Camundongos , Potenciais de Ação/fisiologia , Hipocampo/citologia , Hipocampo/fisiologia , Interneurônios/fisiologia , Neurônios/classificação , Neurônios/fisiologia , Peptídeo Intestinal Vasoativo/metabolismo , Imagem Molecular/métodos , Rodopsina/química , Rodopsina/genética , Proteínas Luminescentes/química , Proteínas Luminescentes/genética , Córtex Visual/citologia , Córtex Visual/fisiologia , Fluorescência , Medições Luminescentes
18.
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
19.
Learn Mem ; 29(9): 302-311, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36206392

RESUMO

The ubiquitin proteasome system (UPS) is a primary mechanism through which proteins are degraded in cells. UPS activity in the dorsal hippocampus (DH) is necessary for multiple types of memory, including object memory, in male rodents. However, sex differences in DH UPS activation after fear conditioning suggest that other forms of learning may also differentially regulate DH UPS activity in males and females. Here, we examined markers of UPS activity in the synaptic and cytoplasmic fractions of DH and medial prefrontal cortex (mPFC) tissue collected 1 h following object training. In males, training increased phosphorylation of proteasomal subunit Rpt6, 20S proteasome activity, and the amount of PSD-95 in the DH synaptic fraction, as well as proteasome activity in the mPFC synaptic fraction. In females, training did not affect measures of UPS or synaptic activity in the DH synaptic fraction or in either mPFC fraction but increased Rpt6 phosphorylation in the DH cytoplasmic fraction. Overall, training-induced UPS activity was greater in males than in females, greater in the DH than in the mPFC, and greater in synaptic fractions than in cytosol. These data suggest that object training drives sex-specific alterations in UPS activity across brain regions and subcellular compartments important for memory.


Assuntos
Condicionamento Clássico , Complexo de Endopeptidases do Proteassoma , Animais , Condicionamento Clássico/fisiologia , Feminino , Hipocampo/fisiologia , Masculino , Camundongos , Córtex Pré-Frontal/fisiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Caracteres Sexuais , Ubiquitina/metabolismo
20.
Int J Mol Sci ; 23(19)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36233148

RESUMO

The search for strategies for strengthening the synaptic efficiency in Aß25-35-treated slices is a challenge for the compensation of amyloidosis-related pathologies. Here, we used the recording of field excitatory postsynaptic potentials (fEPSPs), nitric oxide (NO) imaging, measurements of serine/threonine protein phosphatase (STPP) activity, and the detection of the functional mitochondrial parameters in suspension of brain mitochondria to study the Aß25-35-associated signaling in the hippocampus. Aß25-35 aggregates shifted the kinase-phosphatase balance during the long-term potentiation (LTP) induction in the enhancement of STPP activity. The PP1/PP2A inhibitor, okadaic acid, but not the PP2B blocker, cyclosporin A, prevented Aß25-35-dependent LTP suppression for both simultaneous and delayed enzyme blockade protocols. STPP activity in the Aß25-35-treated slices was upregulated, which is reverted relative to the control values in the presence of PP1/PP2A but not in the presence of the PP2B blocker. A selective inhibitor of stress-induced PP1α, sephin1, but not of the PP2A blocker, cantharidin, is crucial for Aß25-35-mediated LTP suppression prevention. A mitochondrial Na+/Ca2+ exchanger (mNCX) blocker, CGP37157, also attenuated the Aß25-35-induced LTP decline. Aß25-35 aggregates did not change the mitochondrial transmembrane potential or reactive oxygen species (ROS) production but affected the ion transport and Ca2+-dependent swelling of organelles. The staining of hippocampal slices with NO-sensitive fluorescence dye, DAF-FM, showed stimulation of the NO production in the Aß25-35-pretreated slices at the dendrite-containing regions of CA1 and CA3, in the dentate gyrus (DG), and in the CA1/DG somata. NO scavenger, PTIO, or nNOS blockade by selective inhibitor 3Br-7NI partly restored the Aß25-35-induced LTP decline. Thus, hippocampal NO production could be another marker for the impairment of synaptic plasticity in amyloidosis-related states, and kinase-phosphatase balance management could be a promising strategy for the compensation of Aß25-35-driven deteriorations.


Assuntos
Amiloidose , Potenciação de Longa Duração , Proteínas Amiloidogênicas , Cantaridina , Ciclosporina , Hipocampo/fisiologia , Humanos , Potenciação de Longa Duração/fisiologia , Mitocôndrias , Óxido Nítrico , Ácido Okadáico/farmacologia , Fosfoproteínas Fosfatases , Espécies Reativas de Oxigênio , Serina , Trocador de Sódio e Cálcio , Treonina
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