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1.
Cell ; 184(12): 3242-3255.e10, 2021 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-33979655

RESUMEN

Knowing where we are, where we have been, and where we are going is critical to many behaviors, including navigation and memory. One potential neuronal mechanism underlying this ability is phase precession, in which spatially tuned neurons represent sequences of positions by activating at progressively earlier phases of local network theta oscillations. Based on studies in rodents, researchers have hypothesized that phase precession may be a general neural pattern for representing sequential events for learning and memory. By recording human single-neuron activity during spatial navigation, we show that spatially tuned neurons in the human hippocampus and entorhinal cortex exhibit phase precession. Furthermore, beyond the neural representation of locations, we show evidence for phase precession related to specific goal states. Our findings thus extend theta phase precession to humans and suggest that this phenomenon has a broad functional role for the neural representation of both spatial and non-spatial information.


Asunto(s)
Corteza Entorrinal/fisiología , Hipocampo/fisiología , Potenciales de Acción/fisiología , Adulto , Animales , Objetivos , Humanos , Masculino , Neuronas/fisiología , Roedores , Análisis y Desempeño de Tareas , Ritmo Teta/fisiología
2.
Cell ; 180(3): 552-567.e25, 2020 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-32004462

RESUMEN

Cognitive faculties such as imagination, planning, and decision-making entail the ability to represent hypothetical experience. Crucially, animal behavior in natural settings implies that the brain can represent hypothetical future experience not only quickly but also constantly over time, as external events continually unfold. To determine how this is possible, we recorded neural activity in the hippocampus of rats navigating a maze with multiple spatial paths. We found neural activity encoding two possible future scenarios (two upcoming maze paths) in constant alternation at 8 Hz: one scenario per ∼125-ms cycle. Further, we found that the underlying dynamics of cycling (both inter- and intra-cycle dynamics) generalized across qualitatively different representational correlates (location and direction). Notably, cycling occurred across moving behaviors, including during running. These findings identify a general dynamic process capable of quickly and continually representing hypothetical experience, including that of multiple possible futures.


Asunto(s)
Conducta Animal/fisiología , Cognición/fisiología , Toma de Decisiones/fisiología , Hipocampo/fisiología , Potenciales de Acción/fisiología , Animales , Locomoción/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Red Nerviosa/fisiología , Neuronas/fisiología , Ratas , Ratas Long-Evans , Ritmo Teta/fisiología
3.
Cell ; 179(7): 1590-1608.e23, 2019 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-31835034

RESUMEN

Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we show single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution and with repeated sampling over days. In the visual cortex, we use soma-targeted ASAP3 to illustrate cell-type-dependent subthreshold modulation by locomotion. Thus, ASAP3 and ULoVE enable high-speed optical recording of electrical activity in genetically defined neurons at deep locations during awake behavior.


Asunto(s)
Encéfalo/fisiología , Proteínas Activadoras de GTPasa/genética , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Optogenética/métodos , Ritmo Teta , Vigilia , Potenciales de Acción , Animales , Encéfalo/metabolismo , Células CHO , Células Cultivadas , Cricetinae , Cricetulus , Femenino , Proteínas Activadoras de GTPasa/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/metabolismo , Ratas , Ratas Sprague-Dawley , Carrera
4.
Cell ; 175(4): 1119-1130.e15, 2018 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30318145

RESUMEN

Hippocampal theta oscillations were proposed to be important for multiple functions, including memory and temporal coding of position. However, previous findings from bats have questioned these proposals by reporting absence of theta rhythmicity in bat hippocampal formation. Does this mean that temporal coding is unique to rodent hippocampus and does not generalize to other species? Here, we report that, surprisingly, bat hippocampal neurons do exhibit temporal coding similar to rodents, albeit without any continuous oscillations at the 1-20 Hz range. Bat neurons exhibited very strong locking to the non-rhythmic fluctuations of the field potential, such that neurons were synchronized together despite the absence of oscillations. Further, some neurons exhibited "phase precession" and phase coding of the bat's position-with spike phases shifting earlier as the animal moved through the place field. This demonstrates an unexpected type of neural coding in the mammalian brain-nonoscillatory phase coding-and highlights the importance of synchrony and temporal coding for hippocampal function across species.


Asunto(s)
Sincronización Cortical , Hipocampo/fisiología , Animales , Evolución Biológica , Quirópteros , Hipocampo/citología , Interneuronas/fisiología , Masculino , Ratas , Ritmo Teta
5.
Nature ; 629(8012): 630-638, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38720085

RESUMEN

Hippocampal representations that underlie spatial memory undergo continuous refinement following formation1. Here, to track the spatial tuning of neurons dynamically during offline states, we used a new Bayesian learning approach based on the spike-triggered average decoded position in ensemble recordings from freely moving rats. Measuring these tunings, we found spatial representations within hippocampal sharp-wave ripples that were stable for hours during sleep and were strongly aligned with place fields initially observed during maze exploration. These representations were explained by a combination of factors that included preconfigured structure before maze exposure and representations that emerged during θ-oscillations and awake sharp-wave ripples while on the maze, revealing the contribution of these events in forming ensembles. Strikingly, the ripple representations during sleep predicted the future place fields of neurons during re-exposure to the maze, even when those fields deviated from previous place preferences. By contrast, we observed tunings with poor alignment to maze place fields during sleep and rest before maze exposure and in the later stages of sleep. In sum, the new decoding approach allowed us to infer and characterize the stability and retuning of place fields during offline periods, revealing the rapid emergence of representations following new exploration and the role of sleep in the representational dynamics of the hippocampus.


Asunto(s)
Hipocampo , Sueño , Memoria Espacial , Animales , Ratas , Potenciales de Acción/fisiología , Teorema de Bayes , Hipocampo/citología , Hipocampo/fisiología , Aprendizaje por Laberinto/fisiología , Modelos Neurológicos , Neuronas/fisiología , Sueño/fisiología , Memoria Espacial/fisiología , Ritmo Teta/fisiología , Vigilia/fisiología
6.
Nature ; 629(8011): 393-401, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38632400

RESUMEN

Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference1,2. However, how cognitive control regulates working memory storage is unclear. Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta-gamma phase-amplitude coupling (TG-PAC). We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality. We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high. By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour. Our results support a multicomponent architecture of working memory1,2, with frontal control managing maintenance of working memory content in storage-related areas3-5. Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.


Asunto(s)
Hipocampo , Memoria a Corto Plazo , Neuronas , Adulto , Femenino , Humanos , Masculino , Potenciales de Acción , Cognición/fisiología , Lóbulo Frontal/fisiología , Lóbulo Frontal/citología , Ritmo Gamma/fisiología , Hipocampo/fisiología , Hipocampo/citología , Memoria a Corto Plazo/fisiología , Neuronas/fisiología , Lóbulo Temporal/fisiología , Lóbulo Temporal/citología , Ritmo Teta/fisiología , Persona de Mediana Edad
7.
Nature ; 589(7840): 96-102, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33208951

RESUMEN

The hippocampus has a major role in encoding and consolidating long-term memories, and undergoes plastic changes during sleep1. These changes require precise homeostatic control by subcortical neuromodulatory structures2. The underlying mechanisms of this phenomenon, however, remain unknown. Here, using multi-structure recordings in macaque monkeys, we show that the brainstem transiently modulates hippocampal network events through phasic pontine waves known as pontogeniculooccipital waves (PGO waves). Two physiologically distinct types of PGO wave appear to occur sequentially, selectively influencing high-frequency ripples and low-frequency theta events, respectively. The two types of PGO wave are associated with opposite hippocampal spike-field coupling, prompting periods of high neural synchrony of neural populations during periods of ripple and theta instances. The coupling between PGO waves and ripples, classically associated with distinct sleep stages, supports the notion that a global coordination mechanism of hippocampal sleep dynamics by cholinergic pontine transients may promote systems and synaptic memory consolidation as well as synaptic homeostasis.


Asunto(s)
Cuerpos Geniculados/fisiología , Hipocampo/fisiología , Lóbulo Occipital/fisiología , Puente/fisiología , Sueño/fisiología , Ritmo Teta/fisiología , Animales , Emparejamiento Cromosómico/fisiología , Femenino , Homeostasis , Macaca/fisiología , Consolidación de la Memoria/fisiología , Plasticidad Neuronal , Fases del Sueño/fisiología
8.
Nature ; 590(7844): 115-121, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33299180

RESUMEN

Behavioural experiences activate the FOS transcription factor in sparse populations of neurons that are critical for encoding and recalling specific events1-3. However, there is limited understanding of the mechanisms by which experience drives circuit reorganization to establish a network of Fos-activated cells. It is also not known whether FOS is required in this process beyond serving as a marker of recent neural activity and, if so, which of its many gene targets underlie circuit reorganization. Here we demonstrate that when mice engage in spatial exploration of novel environments, perisomatic inhibition of Fos-activated hippocampal CA1 pyramidal neurons by parvalbumin-expressing interneurons is enhanced, whereas perisomatic inhibition by cholecystokinin-expressing interneurons is weakened. This bidirectional modulation of inhibition is abolished when the function of the FOS transcription factor complex is disrupted. Single-cell RNA-sequencing, ribosome-associated mRNA profiling and chromatin analyses, combined with electrophysiology, reveal that FOS activates the transcription of Scg2, a gene that encodes multiple distinct neuropeptides, to coordinate these changes in inhibition. As parvalbumin- and cholecystokinin-expressing interneurons mediate distinct features of pyramidal cell activity4-6, the SCG2-dependent reorganization of inhibitory synaptic input might be predicted to affect network function in vivo. Consistent with this prediction, hippocampal gamma rhythms and pyramidal cell coupling to theta phase are significantly altered in the absence of Scg2. These findings reveal an instructive role for FOS and SCG2 in establishing a network of Fos-activated neurons via the rewiring of local inhibition to form a selectively modulated state. The opposing plasticity mechanisms acting on distinct inhibitory pathways may support the consolidation of memories over time.


Asunto(s)
Red Nerviosa/citología , Red Nerviosa/fisiología , Inhibición Neural , Plasticidad Neuronal/fisiología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Animales , Región CA1 Hipocampal/metabolismo , Colecistoquinina/metabolismo , Conducta Exploratoria/fisiología , Femenino , Ritmo Gamma , Interneuronas/metabolismo , Masculino , Consolidación de la Memoria , Ratones , Parvalbúminas/metabolismo , Células Piramidales/metabolismo , Secretogranina II/genética , Secretogranina II/metabolismo , Navegación Espacial/fisiología , Ritmo Teta
9.
Proc Natl Acad Sci U S A ; 121(25): e2321614121, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38857401

RESUMEN

The medial prefrontal cortex (mPFC) is a key brain structure for higher cognitive functions such as decision-making and goal-directed behavior, many of which require awareness of spatial variables including one's current position within the surrounding environment. Although previous studies have reported spatially tuned activities in mPFC during memory-related trajectory, the spatial tuning of mPFC network during freely foraging behavior remains elusive. Here, we reveal geometric border or border-proximal representations from the neural activity of mPFC ensembles during naturally exploring behavior, with both allocentric and egocentric boundary responses. Unlike most of classical border cells in the medial entorhinal cortex (MEC) discharging along a single wall, a large majority of border cells in mPFC fire particularly along four walls. mPFC border cells generate new firing fields to external insert, and remain stable under darkness, across distinct shapes, and in novel environments. In contrast to hippocampal theta entrainment during spatial working memory tasks, mPFC border cells rarely exhibited theta rhythmicity during spontaneous locomotion behavior. These findings reveal spatially modulated activity in mPFC, supporting local computation for cognitive functions involving spatial context and contributing to a broad spatial tuning property of cortical circuits.


Asunto(s)
Corteza Prefrontal , Ritmo Teta , Corteza Prefrontal/fisiología , Corteza Prefrontal/citología , Animales , Ritmo Teta/fisiología , Masculino , Ratones , Corteza Entorrinal/fisiología , Neuronas/fisiología , Hipocampo/fisiología , Memoria Espacial/fisiología , Ratones Endogámicos C57BL , Memoria a Corto Plazo/fisiología
10.
Proc Natl Acad Sci U S A ; 121(31): e2322869121, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39047043

RESUMEN

Choosing whether to exert effort to obtain rewards is fundamental to human motivated behavior. However, the neural dynamics underlying the evaluation of reward and effort in humans is poorly understood. Here, we report an exploratory investigation into this with chronic intracranial recordings from the prefrontal cortex (PFC) and basal ganglia (BG; subthalamic nuclei and globus pallidus) in people with Parkinson's disease performing a decision-making task with offers that varied in levels of reward and physical effort required. This revealed dissociable neural signatures of reward and effort, with BG beta (12 to 20 Hz) oscillations tracking effort on a single-trial basis and PFC theta (4 to 7 Hz) signaling previous trial reward, with no effects of net subjective value. Stimulation of PFC increased overall acceptance of offers and sensitivity to reward while decreasing the impact of effort on choices. This work uncovers oscillatory mechanisms that guide fundamental decisions to exert effort for reward across BG and PFC, supports a causal role of PFC for such choices, and seeds hypotheses for future studies.


Asunto(s)
Ganglios Basales , Toma de Decisiones , Enfermedad de Parkinson , Corteza Prefrontal , Recompensa , Ritmo Teta , Humanos , Corteza Prefrontal/fisiología , Corteza Prefrontal/fisiopatología , Toma de Decisiones/fisiología , Ganglios Basales/fisiología , Ganglios Basales/fisiopatología , Masculino , Ritmo Teta/fisiología , Femenino , Enfermedad de Parkinson/fisiopatología , Persona de Mediana Edad , Ritmo beta/fisiología , Anciano
11.
Proc Natl Acad Sci U S A ; 120(14): e2218245120, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-36976768

RESUMEN

Our current understanding of brain rhythms is based on quantifying their instantaneous or time-averaged characteristics. What remains unexplored is the actual structure of the waves-their shapes and patterns over finite timescales. Here, we study brain wave patterning in different physiological contexts using two independent approaches: The first is based on quantifying stochasticity relative to the underlying mean behavior, and the second assesses "orderliness" of the waves' features. The corresponding measures capture the waves' characteristics and abnormal behaviors, such as atypical periodicity or excessive clustering, and demonstrate coupling between the patterns' dynamics and the animal's location, speed, and acceleration. Specifically, we studied patterns of θ, γ, and ripple waves recorded in mice hippocampi and observed speed-modulated changes of the wave's cadence, an antiphase relationship between orderliness and acceleration, as well as spatial selectiveness of patterns. Taken together, our results offer a complementary-mesoscale-perspective on brain wave structure, dynamics, and functionality.


Asunto(s)
Ondas Encefálicas , Hipocampo , Animales , Ratones , Hipocampo/fisiología , Encéfalo , Periodicidad , Ritmo Teta
12.
J Neurosci ; 44(4)2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38050110

RESUMEN

Working memory (WM) maintenance relies on multiple brain regions and inter-regional communications. The hippocampus and entorhinal cortex (EC) are thought to support this operation. Besides, EC is the main gateway for information between the hippocampus and neocortex. However, the circuit-level mechanism of this interaction during WM maintenance remains unclear in humans. To address these questions, we recorded the intracranial electroencephalography from the hippocampus and EC while patients (N = 13, six females) performed WM tasks. We found that WM maintenance was accompanied by enhanced theta/alpha band (2-12 Hz) phase synchronization between the hippocampus to the EC. The Granger causality and phase slope index analyses consistently showed that WM maintenance was associated with theta/alpha band-coordinated unidirectional influence from the hippocampus to the EC. Besides, this unidirectional inter-regional communication increased with WM load and predicted WM load during memory maintenance. These findings demonstrate that WM maintenance in humans engages the hippocampal-entorhinal circuit, with the hippocampus influencing the EC in a load-dependent manner.


Asunto(s)
Hipocampo , Memoria a Corto Plazo , Femenino , Humanos , Encéfalo , Electrocorticografía , Corteza Entorrinal , Electroencefalografía , Ritmo Teta
13.
J Neurosci ; 44(24)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38670803

RESUMEN

Despite the known behavioral benefits of rapid eye movement (REM) sleep, discrete neural oscillatory events in human scalp electroencephalography (EEG) linked with behavior have not been discovered. This knowledge gap hinders mechanistic understanding of the function of sleep, as well as the development of biophysical models and REM-based causal interventions. We designed a detection algorithm to identify bursts of activity in high-density, scalp EEG within theta (4-8 Hz) and alpha (8-13 Hz) bands during REM sleep. Across 38 nights of sleep, we characterized the burst events (i.e., count, duration, density, peak frequency, amplitude) in healthy, young male and female human participants (38; 21F) and investigated burst activity in relation to sleep-dependent memory tasks: hippocampal-dependent episodic verbal memory and nonhippocampal visual perceptual learning. We found greater burst count during the more REM-intensive second half of the night (p < 0.05), longer burst duration during the first half of the night (p < 0.05), but no differences across the night in density or power (p > 0.05). Moreover, increased alpha burst power was associated with increased overnight forgetting for episodic memory (p < 0.05). Furthermore, we show that increased REM theta burst activity in retinotopically specific regions was associated with better visual perceptual performance. Our work provides a critical bridge between discrete REM sleep events in human scalp EEG that support cognitive processes and the identification of similar activity patterns in animal models that allow for further mechanistic characterization.


Asunto(s)
Electroencefalografía , Sueño REM , Humanos , Masculino , Femenino , Sueño REM/fisiología , Adulto , Electroencefalografía/métodos , Adulto Joven , Aprendizaje/fisiología , Ritmo Teta/fisiología , Memoria Episódica
14.
J Neurosci ; 44(12)2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38331584

RESUMEN

Cholinergic regulation of hippocampal theta oscillations has long been proposed to be a potential mechanism underlying hippocampus-dependent memory encoding processes. However, cholinergic transmission has been traditionally associated with type II theta under urethane anesthesia. The mechanisms and behavioral significance of cholinergic regulation of type I theta in freely exploring animals is much less clear. In this study, we examined the potential behavioral significance of cholinergic regulation of theta oscillations in the object location task in male mice that involves training and testing trials and provides an ideal behavioral task to study the underlying memory encoding and retrieval processes, respectively. Cholinergic regulation of hippocampal theta oscillations and the behavioral outcomes was examined by either intrahippocampal infusion of cholinergic receptor antagonists or knocking out cholinergic receptors in excitatory neurons or interneurons. We found that both muscarinic acetylcholine receptors (mAChRs) and α7 nicotinic AChRs (α7 nAChRs) regulated memory encoding by engaging excitatory neurons and interneurons, respectively. There is a transient upregulated theta oscillation at the beginning of individual object exploration events that only occurred in the training trials, but not in the testing trials. This transient upregulated theta is also the only theta component that significantly differed between training and testing trials and was sensitive to mAChR and α7 nAChR antagonists. Thus, our study has revealed a transient cholinergic-sensitive theta component that is specifically associated with memory encoding, but not memory retrieval, in the object location task, providing direct experimental evidence supporting a role for cholinergic-regulated theta oscillations in hippocampus-dependent memory encoding processes.


Asunto(s)
Receptores Nicotínicos , Receptor Nicotínico de Acetilcolina alfa 7 , Ratones , Animales , Masculino , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Hipocampo/fisiología , Receptores Nicotínicos/metabolismo , Neuronas/fisiología , Agonistas Nicotínicos/farmacología , Ritmo Teta/fisiología
15.
J Neurosci ; 44(15)2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38395616

RESUMEN

Control over internal representations requires the prioritization of relevant information and suppression of irrelevant information. The frontoparietal network exhibits prominent neural oscillations during these distinct cognitive processes. Yet, the causal role of this network-scale activity is unclear. Here, we targeted theta-frequency frontoparietal coherence and dynamic alpha oscillations in the posterior parietal cortex using online rhythmic transcranial magnetic stimulation (TMS) in women and men while they prioritized or suppressed internally maintained working memory (WM) representations. Using concurrent high-density EEG, we provided evidence that we acutely drove the targeted neural oscillation and TMS improved WM capacity only when the evoked activity corresponded with the desired cognitive process. To suppress an internal representation, we increased the amplitude of lateralized alpha oscillations in the posterior parietal cortex contralateral to the irrelevant visual field. For prioritization, we found that TMS to the prefrontal cortex increased theta-frequency connectivity in the prefrontoparietal network contralateral to the relevant visual field. To understand the spatial specificity of these effects, we administered the WM task to participants with implanted electrodes. We found that theta connectivity during prioritization was directed from the lateral prefrontal to the superior posterior parietal cortex. Together, these findings provide causal evidence in support of a model where a frontoparietal theta network prioritizes internally maintained representations and alpha oscillations in the posterior parietal cortex suppress irrelevant representations.


Asunto(s)
Electroencefalografía , Estimulación Magnética Transcraneal , Masculino , Humanos , Femenino , Ritmo Teta/fisiología , Lóbulo Parietal/fisiología , Corteza Prefrontal/fisiología , Memoria a Corto Plazo/fisiología
16.
J Neurosci ; 44(17)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38438258

RESUMEN

Acetylcholine (ACh) is released from basal forebrain cholinergic neurons in response to salient stimuli and engages brain states supporting attention and memory. These high ACh states are associated with theta oscillations, which synchronize neuronal ensembles. Theta oscillations in the basolateral amygdala (BLA) in both humans and rodents have been shown to underlie emotional memory, yet their mechanism remains unclear. Here, using brain slice electrophysiology in male and female mice, we show large ACh stimuli evoke prolonged theta oscillations in BLA local field potentials that depend upon M3 muscarinic receptor activation of cholecystokinin (CCK) interneurons (INs) without the need for external glutamate signaling. Somatostatin (SOM) INs inhibit CCK INs and are themselves inhibited by ACh, providing a functional SOM→CCK IN circuit connection gating BLA theta. Parvalbumin (PV) INs, which can drive BLA oscillations in baseline states, are not involved in the generation of ACh-induced theta, highlighting that ACh induces a cellular switch in the control of BLA oscillatory activity and establishes an internally BLA-driven theta oscillation through CCK INs. Theta activity is more readily evoked in BLA over the cortex or hippocampus, suggesting preferential activation of the BLA during high ACh states. These data reveal a SOM→CCK IN circuit in the BLA that gates internal theta oscillations and suggest a mechanism by which salient stimuli acting through ACh switch the BLA into a network state enabling emotional memory.


Asunto(s)
Acetilcolina , Colecistoquinina , Ratones Endogámicos C57BL , Ritmo Teta , Ritmo Teta/efectos de los fármacos , Ritmo Teta/fisiología , Animales , Masculino , Ratones , Femenino , Acetilcolina/farmacología , Acetilcolina/metabolismo , Colecistoquinina/farmacología , Colecistoquinina/metabolismo , Interneuronas/fisiología , Interneuronas/efectos de los fármacos , Somatostatina/metabolismo , Somatostatina/farmacología , Amígdala del Cerebelo/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Complejo Nuclear Basolateral/fisiología , Complejo Nuclear Basolateral/efectos de los fármacos , Red Nerviosa/fisiología , Red Nerviosa/efectos de los fármacos , Receptor Muscarínico M3/fisiología , Receptor Muscarínico M3/metabolismo , Parvalbúminas/metabolismo
17.
Mol Psychiatry ; 29(2): 327-341, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38123729

RESUMEN

Hypocretin/Orexin (HCRT/OX) and dopamine (DA) are both key effectors of salience processing, reward and stress-related behaviors and motivational states, yet their respective roles and interactions are poorly delineated. We inactivated HCRT-to-DA connectivity by genetic disruption of Hypocretin receptor-1 (Hcrtr1), Hypocretin receptor-2 (Hcrtr2), or both receptors (Hcrtr1&2) in DA neurons and analyzed the consequences on vigilance states, brain oscillations and cognitive performance in freely behaving mice. Unexpectedly, loss of Hcrtr2, but not Hcrtr1 or Hcrtr1&2, induced a dramatic increase in theta (7-11 Hz) electroencephalographic (EEG) activity in both wakefulness and rapid-eye-movement sleep (REMS). DAHcrtr2-deficient mice spent more time in an active (or theta activity-enriched) substate of wakefulness, and exhibited prolonged REMS. Additionally, both wake and REMS displayed enhanced theta-gamma phase-amplitude coupling. The baseline waking EEG of DAHcrtr2-deficient mice exhibited diminished infra-theta, but increased theta power, two hallmarks of EEG hyperarousal, that were however uncoupled from locomotor activity. Upon exposure to novel, either rewarding or stress-inducing environments, DAHcrtr2-deficient mice featured more pronounced waking theta and fast-gamma (52-80 Hz) EEG activity surges compared to littermate controls, further suggesting increased alertness. Cognitive performance was evaluated in an operant conditioning paradigm, which revealed that DAHcrtr2-ablated mice manifest faster task acquisition and higher choice accuracy under increasingly demanding task contingencies. However, the mice concurrently displayed maladaptive patterns of reward-seeking, with behavioral indices of enhanced impulsivity and compulsivity. None of the EEG changes observed in DAHcrtr2-deficient mice were seen in DAHcrtr1-ablated mice, which tended to show opposite EEG phenotypes. Our findings establish a clear genetically-defined link between monosynaptic HCRT-to-DA neurotransmission and theta oscillations, with a differential and novel role of HCRTR2 in theta-gamma cross-frequency coupling, attentional processes, and executive functions, relevant to disorders including narcolepsy, attention-deficit/hyperactivity disorder, and Parkinson's disease.


Asunto(s)
Cognición , Neuronas Dopaminérgicas , Electroencefalografía , Receptores de Orexina , Vigilia , Animales , Ratones , Neuronas Dopaminérgicas/fisiología , Neuronas Dopaminérgicas/metabolismo , Cognición/fisiología , Receptores de Orexina/metabolismo , Receptores de Orexina/fisiología , Vigilia/fisiología , Masculino , Electroencefalografía/métodos , Nivel de Alerta/fisiología , Ratones Endogámicos C57BL , Ratones Noqueados , Orexinas/metabolismo , Orexinas/fisiología , Sueño REM/fisiología , Transducción de Señal/fisiología , Ritmo Teta/fisiología , Recompensa , Dopamina/metabolismo
18.
PLoS Biol ; 20(1): e3001546, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35100261

RESUMEN

The subiculum is positioned at a critical juncture at the interface of the hippocampus with the rest of the brain. However, the exact roles of the subiculum in most hippocampal-dependent memory tasks remain largely unknown. One obstacle to make comparisons of neural firing patterns between the subiculum and hippocampus is the broad firing fields of the subicular cells. Here, we used spiking phases in relation to theta rhythm to parse the broad firing field of a subicular neuron into multiple subfields to find the unique functional contribution of the subiculum while male rats performed a hippocampal-dependent visual scene memory task. Some of the broad firing fields of the subicular neurons were successfully divided into multiple subfields similar to those in the CA1 by using the theta phase precession cycle. The new paradigm significantly improved the detection of task-relevant information in subicular cells without affecting the information content represented by CA1 cells. Notably, we found that multiple fields of a single subicular neuron, unlike those in the CA1, carried heterogeneous task-related information such as visual context and choice response. Our findings suggest that the subicular cells integrate multiple task-related factors by using theta rhythm to associate environmental context with action.


Asunto(s)
Potenciales de Acción/fisiología , Región CA1 Hipocampal/fisiología , Memoria/fisiología , Neuronas/fisiología , Ritmo Teta/fisiología , Algoritmos , Animales , Región CA1 Hipocampal/anatomía & histología , Masculino , Aprendizaje por Laberinto/fisiología , Neuronas/citología , Reconocimiento Visual de Modelos/fisiología , Ratas , Ratas Long-Evans
19.
Cereb Cortex ; 34(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39110414

RESUMEN

Adaptive behavior is fundamental to cognitive control and executive functioning. This study investigates how cognitive control mechanisms and episodic feature retrieval interact to influence adaptiveness, focusing particularly on theta (4 to 8 Hz) oscillatory dynamics. We conducted two variations of the Simon task, incorporating response-incompatible, response-compatible, and neutral trials. Experiment 1 demonstrated that cognitive adjustments-specifically, cognitive shielding following incompatible trials and cognitive relaxation following compatible ones-are reflected in midfrontal theta power modulations associated with the Simon effect. Experiment 2 showed that reducing feature overlap between trials leads to less pronounced sequential modulations in behavior and midfrontal theta activity, supporting the hypothesis that cognitive control and feature integration share a common neural mechanism. These findings highlight the interaction of cognitive control processes and episodic feature integration in modulating behavior. The results advocate for hybrid models that combine top-down and bottom-up processes as a comprehensive framework to understand cognitive control dynamics and adaptive behavior.


Asunto(s)
Cognición , Conflicto Psicológico , Función Ejecutiva , Ritmo Teta , Humanos , Ritmo Teta/fisiología , Masculino , Femenino , Adulto Joven , Cognición/fisiología , Adulto , Función Ejecutiva/fisiología , Tiempo de Reacción/fisiología , Electroencefalografía , Desempeño Psicomotor/fisiología , Adaptación Psicológica/fisiología , Encéfalo/fisiología
20.
Cereb Cortex ; 34(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38976973

RESUMEN

Joint attention is an indispensable tool for daily communication. Abnormalities in joint attention may be a key reason underlying social impairment in schizophrenia spectrum disorders. In this study, we aimed to explore the attentional orientation mechanism related to schizotypal traits in a social situation. Here, we employed a Posner cueing paradigm with social attentional cues. Subjects needed to detect the location of a target that is cued by gaze and head orientation. The power in the theta frequency band was used to examine the attentional process in the schizophrenia spectrum. There were four main findings. First, a significant association was found between schizotypal traits and attention orientation in response to invalid gaze cues. Second, individuals with schizotypal traits exhibited significant activation of neural oscillations and synchrony in the theta band, which correlated with their schizotypal tendencies. Third, neural oscillations and synchrony demonstrated a synergistic effect during social tasks, particularly when processing gaze cues. Finally, the relationship between schizotypal traits and attention orientation was mediated by neural oscillations and synchrony in the theta frequency band. These findings deepen our understanding of the impact of theta activity in schizotypal traits on joint attention and offer new insights for future intervention strategies.


Asunto(s)
Atención , Señales (Psicología) , Esquizofrenia , Ritmo Teta , Humanos , Masculino , Femenino , Ritmo Teta/fisiología , Atención/fisiología , Adulto Joven , Esquizofrenia/fisiopatología , Adulto , Electroencefalografía , Trastorno de la Personalidad Esquizotípica/fisiopatología , Psicología del Esquizofrénico
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