Biology subjects

Fuentealba, P.

Publications and source records attributed to Fuentealba, P..

13 recordsLinked to original sources

bioRxiv2026

Responsiveness of cerebral cortex to hippocampal inputs depends on brain region and brain state

Gamma oscillations (30-90 Hz) are a prominent signature of cortical network state, but whether they facilitate or hinder inter-areal communication remains unresolved. The communication-through-coherence hypothesis posits that gamma enhances transmission between areas, whereas recent computational work suggests that high-amplitude gamma oscillations may instead filter incoming inputs and reduce their impact. To distinguish between these accounts, we used a well-defined physiological input--sharp-wave ripple (SWR) complexes--to probe cortical responsiveness via two parallel monosynaptic pathways: from ventral CA1 to prefrontal cortex (PFC), and from dorsal CA1 to retrosplenial cortex (RSC). By classifying the cortical state immediately preceding each ripple as low- or high-amplitude gamma, we found that PFC responses to ripples were significantly larger during low-amplitude gamma states, an effect carried by the ventral CA1-PFC pathway and driven primarily by ripples during quiet wakefulness. RSC showed no such state-dependent modulation. A mean-field model of PFC reproduced the enhanced responsiveness during low-amplitude gamma and revealed that this modulation depends on the excitatory-inhibitory balance of the afferent input and on the level of recurrent excitation--providing a mechanistic explanation for the distinct behaviors of PFC and RSC, which differ in their local recurrent connectivity. Extending the model to a chain of cortical areas predicted that low-amplitude gamma supports robust propagation of activity across regions, whereas high-amplitude gamma confines it locally. Together, these results argue that low-amplitude gamma, rather than strong gamma synchronization, constitutes a favorable substrate for communication between brain areas.

neuroscience↗

bioRxiv2026

Multimodal Alignment of MicroCT Imaging to Vibroacoustic Signals to Validate Soft Tissue Needle Transitions in Manduca sexta

ObjectiveRobotic-assisted needle insertions lack haptic feedback, a key sensory cue for detecting tissue transitions and regulating puncture force. Modeling this feedback requires an understanding of soft-tissue biomechanics during insertion. Vibroacoustic signals generated by needle-tissue interactions may provide an additional sensing modality, but their interpretation requires validation against anatomical ground truth. MethodsA multimodal framework was developed to correlate vibroacoustic signals with high-resolution post-puncture microCT ({micro}CT) imaging in Manduca sexta, an insect model containing interconnected soft-tissue layers. A custom clip-on prototype recorded vibroacoustic signals during manual needle insertions. Three trajectory-marking strategies were evaluated to determine 3D coordinates of soft-tissue layer crossings and to assess correlations between acoustic events and anatomical transitions. Distances between layer crossings and needle displacement were used for spatiotemporal alignment of vibroacoustic and {micro}CT data. ResultsA {micro}CT-compatible nylon string preserved puncture trajectories without artifacts and enabled high-resolution 3D reconstruction of anatomy and needle paths. Fusion of vibroacoustic and imaging data allowed identification of acoustic events associated with tissue entry, exit, and transitions. ConclusionBy integrating high-resolution {micro}CT imaging with vibroacoustic sensing, this study establishes a biologically grounded framework for validating the relationship between vibroacoustic signals and anatomical tissue transitions during needle insertion, providing a basis for future quantitative analyses. SignificanceThis work provides initial evidence for correlating vibroacoustic signals recorded during needle insertion with corresponding {micro}CT-identified tissue barriers. Because vibroacoustics offers substantially higher temporal and spatial resolution than most imaging modalities, it has the potential to improve tissue sensing and procedural accuracy in future needle-based interventions.

biophysics↗

bioRxiv2026

Global Neural Oscillations Underlie Performance Variability and Attentional State Fluctuations in Humans

Fluctuations in attentional states, such as mind-wandering (MW), are associated with critical variability in task performance. While fMRI studies highlight the opposing roles of task-positive (e.g., dorsal attention network) and task-negative (e.g., default mode network) systems, the electrophysiological mechanisms underlying these dynamics remain poorly understood. Using intracranial electrocorticography in humans performing a sustained attention task, we identified global oscillatory dynamics linked to attentional shifts. MW was characterized by (i) reduced theta ({theta}) and alpha ({square}) power, (ii) decreased aperiodic signal components, indicating a shift toward cortical inhibition, (iii) enhanced phase synchronization across networks, and (iv) strengthened {theta} phase-behavior correlations ({rho}). These features support a non-network-specific framework in which low-frequency {theta} dynamics--captured by both {theta} power and {rho}--are associated with attentional fluctuations, while aperiodic offset relates to attentional state indirectly through its association with {rho} (Structural Equation Modeling: power[->]state {beta} = -0.118, p = 0.002; {rho}[->]state {beta} = 0.246, p < 0.001; offset[->]{rho} {beta} = -0.222, p < 0.001). Our study provides a unified neurophysiological framework for understanding how spontaneous neural activity can drive attentional fluctuations and performance variability, with implications for research on attention, learning, and neuropsychiatric disorders.

neuroscience↗

bioRxiv2026

Infraslow modulation of theta synchrony in the hippocampus circuit during REM sleep

Sleep dynamically reorganizes hippocampal activity, but how this reconfiguration supports large-scale coordination across the hippocampal circuit remains unclear. We performed simultaneous recordings from dorsal (CA1d) and ventral (CA1v) hippocampus, retrosplenial cortex (RSC), prefrontal cortex (PFC), and dorsal thalamus in rats across brain states. Theta oscillations dominated hippocampal activity during active behaviour and REM sleep, while delta oscillations prevailed during nREM and quiet waking. Phase synchrony between CA1d and CA1v varied across states, peaking during REM sleep and exhibiting infraslow fluctuations (0.02 Hz) unique to this stage. These slow modulations persisted after controlling for theta power, suggesting a genuine modulation of interregional synchrony. Transitions into REM were marked by rising CA1d-CA1v synchrony and widespread neuronal activation, with thalamic activity most strongly predicting coupling dynamics. During REM sleep, neuronal firing across hippocampal-cortical-thalamic circuits was phase-locked to the infraslow theta coupling cycle, indicating gain modulation at the network level. Such entrainment was strongest and most consistent in REM and aligned near a common phase, revealing temporally structured communication at multiple scales. Our findings identify an infraslow modulation of hippocampal theta coherence that temporally organizes neuronal excitability across brain regions during REM sleep, offering a systems-level mechanism for regulating inter-regional communication during sleep.

neuroscience↗

bioRxiv2026

Spatial memory performance is associated with region-specific coordination of hippocampo-cortical sleep oscillations

Sleep plays a critical role in memory consolidation, yet how coordination among sleep oscillations across hippocampo-cortical circuits relates to behavioral performance remains incompletely understood. Here, we examined how cross-regional coordination of cardinal sleep oscillations during non-rapid eye movement (nREM) sleep relates to spatial memory performance. Adult rats were trained in an object-place recognition task and allowed to sleep while local field potentials were recorded simultaneously from dorsal and ventral hippocampus (CA1d and CA1v) and retrosplenial, prefrontal, and lateral entorhinal cortices. We first confirm that nREM sleep duration, but not REM sleep, is positively associated with spatial memory performance. We then characterized the temporal relationships between hippocampal sharp-wave ripples and cortical spindles and slow oscillations, revealing region- and oscillation-specific coordination patterns that depend on the dorso-ventral origin of hippocampal ripple events. Finally, by comparing task-related changes in ripple-triggered cortical activity between low- and high-performing sessions, we identify selective, performance-dependent modulation of hippocampo-cortical coupling during task-related sleep. Spatial memory performance was consistently associated with enhanced ripple-spindle and ripple-slow oscillation coupling driven by dorsal hippocampal ripples, particularly in interactions with entorhinal and prefrontal cortices, whereas ventral hippocampal interactions failed to show behavioural association. Together, these results reveal that spatial memory performance is linked to region- and timing-specific coordination of sleep oscillations across hippocampo-cortical networks during nREM sleep, highlighting a functional differentiation of dorsal and ventral hippocampal contributions to sleep-dependent memory consolidation.

neuroscience↗

bioRxiv2025

Crossfrequency routing in a hippocampocortical circuit during probabilistic reversal learning

Learning under uncertainty requires detecting latent changes in environmental contingencies and flexibly adjusting choice strategy. To model this process and identify associated circuit dynamics, we trained rats on a two-armed bandit task with uncued reward reversals while simultaneously recording local field potentials from the circuit comprised by dorsal hippocampus (CA1d), lateral entorhinal cortex (LEC), and prefrontal cortex (PFC). Behavioral performance improved with training and progressively shifted from outcome-reactive exploration to an exploitation-biased strategy, quantified using a model-free index. Mixed-effects modeling combining behavioral and neural metrics identified tonic cortical synchrony in theta and fast-gamma bands as a negative session-scale performance marker. Theta and gamma oscillations were coordinated, as cross-regional phase-amplitude coupling showed that CA1d theta phase gated fast-gamma activity in PFC, while biasing both slow- and fast-gamma bursts in LEC, which selectively increased at goal-reaching. Neuronal spiking showed cross-regional phase-locking to both theta and gamma rhythms, indicating synchronized timing across the hippocampo-cortical circuit. Finally, distributed neuronal spiking across the circuit represented goal-approach, yet only prefrontal neurons ramped during goal-reaching, suggesting a role in outcome assessment, while hippocampal and entorhinal units transiently suppressed, consistent with locomotor tracking and resetting. These results reveal a tonic cortical connectivity marker of ongoing performance during reversal learning and dissociate it from hippocampal theta mechanisms that selectively organize cortical gamma bursts and spike timing. Together, these results provide mechanistic insight into how frequency-specific hippocampo-cortical interactions dynamically reconfigure to support strategy transitions, offering a circuit-level framework for understanding adaptive decision-making under uncertainty. Significance StatementAnimals often learn in uncertain environments, where they must decide whether to keep exploiting a known option or explore alternatives. We trained rats on a probabilistic choice task while recording brain activity from hippocampus, entorhinal cortex, and prefrontal cortex. We found that performance improvements were linked to an ongoing interaction between entorhinal and prefrontal areas, whereas hippocampal signals changed mainly with training and controlled the timing of brief, fast activity bursts in cortex. Near reward, prefrontal neurons ramped up while hippocampal and entorhinal neurons were suppressed. Together, these results separate brain signals that track current performance from those that shape cortical dynamics during learning.

neuroscience↗

bioRxiv2025

Hippocampo-supramammillary coupling across sleep and wake

Hippocampal communication with subcortical circuits reorganizes across sleep-wake states, yet the dynamics of such interactions remain incompletely defined. We simultaneously recorded neuronal spiking and local field potentials from the dorsal hippocampus (CA1 and dentate gyrus) and limbic subcortical nuclei (supramammillary nucleus (SuM) and lateral septum (LS)) in freely behaving rats across the sleep-wake cycle. During quiescent states (non-rapid eye movement (nREM) sleep and quiet wakefulness), sharp-wave ripples dominated hippocampal activity and produced fast, top-down excitation, with large population surges locally in CA1 and DG, and more modest but significant activation in LS and SuM, whereas dentate spikes elicited smaller state-invariant responses. Conversely, in the bottom-up direction, epochs of high-discharge SuM activity were associated with slower, state-dependent activation of hippocampal populations that was larger in wake than in sleep, revealing distinct temporal scales and state dependence for reciprocal pathways. During activated, theta-enriched states (rapid eye movement (REM) sleep and active wakefulness), spike-field coupling revealed circuit-wide theta coordination. In active wakefulness, SuM bursts produced brief inhibition of CA1 spiking while theta oscillations organized a multiregional firing sequence around the theta cycle trough; yet SuM neurons were not significantly phase-locked. In REM sleep, this pattern inverted, with only SuM neurons significantly phase-locking to theta waves, and preferred firing near the theta cycle peak. Together, these findings identify state-dependent, bidirectional coordination between hippocampus and subcortical nuclei, characterized by ripple-locked top-down hippocampal output during quiescent states and SuM-mediated bottom-up modulation that reconfigures under theta during activated states.

neuroscience↗

bioRxiv2025

Hippocampal Synchrony Dynamically Gates Cortical Connectivity Across Brain States

Memory consolidation is thought to rely on hippocampo-cortical dialogue orchestrated by three cardinal sleep oscillations: cortical slow oscillations, thalamic spindles, and hippocampal sharp-wave ripples. However, how hippocampal outputs are routed to specific cortical targets and dynamically regulated across brain states remains incompletely understood. Here, we performed simultaneous multisite recordings from the dorsal and ventral hippocampus, and frontal and parietal cortex in rats alternating between wakefulness and sleep. Frontal slow oscillations operated as a global clock, resetting thalamic circuits and initiating spindle volleys that propagated from anterior to posterior cortex, while parietal slow oscillations more effectively recruited hippocampal ripples. Hippocampal ripples reflected anatomical connectivity, as dorsal ripples preferentially enhanced parietal spindles, whereas ventral ripples engaged mainly frontal spindling. Notably, when ripples synchronized in dorsal and ventral hippocampus, local excitatory drive sharply decreased and neuronal spiking redistributed, associated cortical slow oscillations and spindle responses diminished, and cortical neuronal reactivation was suppressed, indicating that dorso-ventral ripple synchrony gates, rather than amplifies, hippocampo-cortical communication. This gating effect was most evident through interactions with brain state, as dorsal-driven reactivation persisted across vigilance states, while ventral pathways were more pronounced during sleep. Collectively, our results outline a multilayer architecture in which slow oscillations provide a global temporal scaffold, spindles implement anatomically specific reactivation channels, and ripple coordination gates hippocampo-cortical communication, likely shaping the precision and specificity of memory consolidation within a highly variable neural substrate. SignificanceSharp-wave ripples in the hippocampus are critical for memory consolidation, in part due to their precise temporal coordination with cortico-thalamic sleep rhythms. However, whether ripple synchronization along the hippocampal septo-temporal axis modulates cortical memory processing has remained unresolved. Here, we show that coordinated ripples, occurring simultaneously in dorsal and ventral CA1, are observed more frequently than predicted by independent occurrence and are associated with significant suppression of cortical reactivation compared to isolated episodes. This suppression does not reflect simple changes in ripple structure or increased inhibition, but instead is linked to a redistribution of excitatory drive across the hippocampal septo-temporal axis. Importantly, this gating effect is present across both sleep and wakefulness. These findings suggest that hippocampal synchrony dynamically gates, rather than amplifies, cortical engagement, thus refining systems consolidation models by highlighting the significance of network organization and precise temporal dynamics in shaping memory replay.

neuroscience↗

bioRxiv2024

Synchronization of the prefrontal cortex with the hippocampus and posterior parietal cortex is navigation strategy-dependent during spatial learning

1.During goal-directed spatial learning, subjects progressively change their navigation strategies to increase their navigation efficiency, an operation supported by the medial prefrontal cortex (mPFC). However, how the mPFC may integrate relevant information in a wider memory networks involving the hippocampus (HPC) and the posterior parietal cortex (PPC) is poorly understood. We recorded local-field potential and neuronal firing simultaneously from the mPFC, HPC and PPC in mice subjected to spatial memory acquisition in the Barnes maze. During navigation trials, animals demonstrated two consecutive behavioral stages: searching and exploration. Throughout training, mice gradually switched from less efficient (non-spatial) to more efficient (spatial) goal-oriented strategies exclusively during the searching stage. 4-Hz and theta (6-12 Hz) oscillations were detected during spatial navigation in the three recorded areas associated with episodes of immobility and locomotion, respectively. The entrainment of prefrontal gamma oscillations (60-100 Hz) by hippocampal and parietal 4-Hz and theta oscillations, as well as the incidence of prefrontal gamma, was higher when mice implemented spatial strategies during the searching stage. Interestingly, 4-Hz and theta from HPC and PPC also synchronized the spike-timing of prefrontal neurons, which was maximum during spatial strategies in the searching stage. Finally, neurons recorded in the mPFC increased their task stage firing selectivity when they used spatial strategy. Altogether, these results provide evidence for the neural mechanisms underlying the prefrontal large-scale coordination with distributed neural networks during spatial learning.

neuroscience↗

bioRxiv2022

Optogenetic stimulation of septal somatostatin neurons disrupts locomotory behavior and regulates hippocampus cholinergic theta oscillations

The septal complex regulates both motivated and innate behaviors, chiefly by the action of its diverse population of long-range projection neurons. Among those cells are lateral septum somatostatin neurons which collateral axons profusely innervate cortically-projecting neurons located in the medial septum. Thus, somatostatin cells are ideally positioned at the crossroads of ascending and descending modulatory pathways, likely supporting functional roles in both anatomical directions. Here, we used optogenetic stimulation and extracellular recordings in acutely anesthetized transgenic mice to show that septal somatostatin neurons can disinhibit the cholinergic septo-hippocampal pathway, thus enhancing the amplitude and synchrony of theta oscillations, while depressing sharp wave ripple episodes in the dorsal hippocampus. Nonetheless, photosuppressing septal somatostatin cells hindered goal-directed behavior in a spatial memory task by disrupting task engagement, evidenced in increased immobility, followed by repetitive self-grooming, a hallmark innate behavior. These results suggest that septal somatostatin cells can recruit ascending cholinergic pathways to promote hippocampal theta oscillations, while gating repetitive displacement behaviors mediated by descending subcortical pathways. Significance StatementA small population of somatostatin-expressing GABAergic cells in the lateral septum projects deep into subcortical regions, yet on its way it also targets neighboring medial septum neurons that profusely innervate cortical targets. We show here that selective inhibition of septal somatostatin cells exerts significant consequences in both ascending and descending synaptic pathways. Indeed, cortical targets increased the expression of hippocampal theta oscillations, which are relevant for sensorimotor processing, temporal coding, and a marker of anxious behaviour; whereas subcortical targets triggered repetitive self-grooming, an innate displacement behaviour. Our results suggest that septal somatostatin cells are a potential target for the control of altered innate behaviors in translational neuroscience.

neuroscience↗

bioRxiv2020

Cortical dynamics underlying social behavior in dominance hierarchy and spatial navigation

Rodents establish dominance hierarchy as a social ranking system in which one subject acts as dominant over all the other subordinate individuals. Dominance hierarchy regulates food access and mating opportunities, but little is known of its significance in collective behavior, for instance during navigation for foraging or migration. Here, we implemented a simplified goal-directed spatial navigation task in mice and found that the social context exerts significant influence on individual decision-making, even when efficient navigation rules leading to reward had been previously learned. Thus, decision-making and consequent task performance were strongly dependent on contingent social interactions arising during collective navigation, yet their influence on individual behavior was outlined by dominance hierarchy. Dominant animals did not behave as leaders during navigation; conversely, they were most sensitive to social context. Social ranking in turn was reflected in the neural activity and connectivity patterns of the prefrontal cortex and hippocampus, both in anesthetized and behaving mice. These results suggest that the interplay between contingent social interactions and dominance hierarchy can regulate behavioral performance, supported by the intrinsic matrix of coordinated activity in the hippocampal-prefrontal circuit. Significance StatementDecision-making is shaped by intrinsic features, such as memory-stored information, and external influences, such as social interactions, yet their interplay is not well understood. We studied decision-making during collective behavior and found that instead of prioritizing memory-based pertinent information, mice shifted their individual decisions according to contingent social interactions arising in the social context. Conversely, constitutive social interactions, such as dominance hierarchy, were relevant to outline the effect of the social environment on individual behavior. Our results suggest that intrinsic hippocampal-cortical activity and connectivity patterns define social interactions. Hence, intrinsic cortical dynamics underlie behavioral performance during social decision-making.

neuroscience↗

bioRxiv2019

Dentate gyrus somatostatin cells are required for contextual discrimination during episodic memory encoding

Episodic memory establishes and stores relations among the different elements of an experience, which are often similar and difficult to distinguish. Pattern separation, implemented by the dentate gyrus, is a neural mechanism that allows the discrimination of similar experiences by orthogonalizing synaptic inputs. Granule cells support such disambiguation by sparse rate coding, a process tightly controlled by highly diversified GABAergic neuronal populations, such as somatostatin-expressing cells which directly target the dendritic arbor of granule cells, massively innervated by entorhinal inputs reaching the molecular layer and conveying contextual information. Here, we tested the hypothesis that somatostatin neurons regulate the excitability of the dentate gyrus, thus controlling the efficacy of pattern separation during memory encoding in mice. Indeed, optogenetic suppression of dentate gyrus somatostatin neurons increased spiking activity in putative excitatory neurons and triggered dentate spikes. Moreover, optical inhibition of somatostatin neurons impaired both contextual and spatial discrimination of overlapping episodic-like memories during task acquisition. Importantly, effects were specific for similar environments, suggesting that pattern separation was selectively engaged when overlapping conditions ought to be distinguished. Overall, our results suggest that somatostatin cells regulate excitability in the dentate gyrus and are required for effective pattern separation during episodic memory encoding.\n\nSignificance statementMemory systems must be able to discriminate stored representations of similar experiences in order to efficiently guide future decisions. This is solved by pattern separation, implemented in the dentate gyrus by granule cells to support episodic memory formation. The tonic inhibitory bombardment produced by multiple GABAergic cell populations maintains low activity levels in granule cells, permitting the process of pattern separation. Somatostatin-expressing cells are one of those interneuron populations, selectively targeting the distal dendrites of granule cells, where cortical multimodal information reaches the dentate gyrus. Hence, somatostatin cells constitute an ideal candidate to regulate pattern separation. Here, by using optogenetic stimulation in mice, we demonstrate that somatostatin cells are required for the acquisition of both contextual and spatial overlapping memories.

neuroscience↗

bioRxiv2017

Basal forebrain gating by somatostatin neurons drives cortical activity

The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing cells constitute a local GABAergic source known to functionally inhibit the major cortically-projecting cell types. However, it remains unclear if somatostatin cells can regulate the basal forebrains synaptic output and thus control cortical dynamics. Here, we demonstrate in mice that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo increased spiking of some basal forebrain cells, rapidly enhancing and desynchronizing neural activity in the prefrontal cortex, inhibiting slow rhythms and increasing gamma oscillations. Locomotor activity was specifically increased in quiescent animals, but not in active mice. Altogether, we provide physiological and behavioral evidence indicating that somatostatin cells are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms.

neuroscience↗