Biology subjects

Lazcano, G.

Publications and source records attributed to Lazcano, G..

6 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

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↗