bioRxiv Science⌕ Search

Biology subjects

Eschenko, O.

Publications and source records attributed to Eschenko, O..

5 recordsLinked to original sources

Hippocampus-reuniens beta coupling supports goal-directed spatial navigation

Prefrontal-hippocampal communication, supported by both direct and indirect anatomical pathways, is essential for a range of cognitive functions, including spatial navigation. The midline thalamic nucleus reuniens (RE) has been proposed as a key hub along this indirect pathway, coordinating bidirectional interactions between the hippocampus (HC) and prefrontal cortex (PFC). Here, we investigated functional dynamics within the HC-RE-PFC network as adult male rats learned to navigate a complex maze. Initial behavioral analyses revealed three distinct learning phases: exploration, goal-oriented learning, and efficient navigation. Aligning neural data with subject-specific transitions between these phases uncovered distinct neural signatures associated with each learning phase. Notably, the transition from exploratory to goal-directed behavior was accompanied by the emergence of persistent HC-RE beta-band (15-25Hz) interactions, including elevated beta coherence, theta-beta phase-amplitude coupling, and HC-to-RE Granger causality. The interactions further scaled with navigational efficiency, showing increased HC-RE beta coherence in trials without errors. Together, these findings provide new evidence for dynamic HC-RE interactions during goal-directed navigation and support an emerging view that RE functions as a working memory buffer for route-related information, revealing a potential network mechanism underlying flexible spatial behavior. HighlightsO_LIBeta-band hippocampus-reuniens coupling emerges during goal-directed navigation. C_LIO_LIPAC between HC theta and RE beta increased during goal learning. C_LIO_LIHC-RE coupling strength increases with navigational efficiency. C_LIO_LIDirectional hippocampus-to-reuniens communication emerges during learning C_LIO_LIReuniens supports hippocampal-prefrontal integration for flexible behavior C_LI Significance StatementFlexible spatial navigation requires coordinated communication between the hippocampus (HC) and the prefrontal cortex (PFC), yet the thalamic mechanisms coordinating HC-PFC interaction remain poorly understood. This study reveals that the nucleus reuniens (RE) of the midline thalamus plays a critical role in mediating HC-PFC communication during spatial learning. By combining detailed behavioral analysis with simultaneous multi-site electrophysiological recording, we identify beta-band HC-RE coupling as a neural signature of the transition from exploration to goal-directed navigation. The strength and directionality of this interaction tracked improvements in navigational efficiency, revealing a thalamic mechanism for integrating hippocampal output into prefrontal circuits. These findings highlight the RE as a working memory buffer for route-related information and advance our understanding of how thalamic hubs contribute to the circuit-level dynamics underlying flexible behavior.

neuroscience↗

Spontaneous locus coeruleus bursts coincide withtransient global brain state changes similar to thoseelicited by surprise

Sudden and isolated sensory stimuli (SISS) engage the extralemniscal system and elicit widespread electrocortical responses in the brain. These responses, consisting of both time-domain transients and spectral changes, reflect a switch of the global brain state that likely prepares the organism for subsequent urgent behaviours. Crucially, SISS also elicit a short-latency phasic response in a key component of the extralemniscal system in the brainstem, the noradrenergic Locus Coeruleus (LC) nucleus. Such stimulus-evoked LC firing is associated with the electrocortical markers of extralemniscal activation. LC neurons also display burst-like firing spontaneously, i.e., without imposed sensory stimuli, for example, during quiet wakefulness, sleep, or anaesthesia. However, this phenomenon remains underexplored. We therefore measured, in freely behaving rats, the prefrontal electrocorticogram (ECoG) responses following spontaneous LC bursts. In addition, we compared these ECoG responses to those triggered by electrical LC stimulation or auditory SISS. We found that ECoG responses were proportional to the magnitude of the spontaneous LC bursts or microstimulation, and remarkably similar to those elicited by SISS. Finally, suppression of noradrenergic transmission with systemic clonidine administration attenuated the auditory-evoked ECoG response. These results suggest that LC plays a role in generating the transient brain state changes elicited by SISS.

neuroscience↗

Differential locus coeruleus-hippocampus interactions during offline states

Patterns of locus coeruleus (LC) activity and norepinephrine (NE) release during non-rapid-eye-movement (NREM) sleep suggest a critical role for the LC-NE system in offline modulation of forebrain circuits. NE transmission promotes synaptic plasticity and is required for memory consolidation, but the field has only begun to uncover how LC activity contributes to coordinated forebrain network dynamics. Hippocampal ripples, a hallmark of memory replay, are temporally coupled with thalamocortical oscillations; however, the circuit mechanisms underlying systems-level consolidation across larger brain networks remain incompletely understood. Here, using multi-site electrophysiology, we examined LC firing in relation to hippocampal ripples in freely behaving rats. LC activity and ripple occurrence were state-dependent and inversely related: heightened arousal was associated with increased LC firing and reduced ripple rates. At finer timescales, LC spiking decreased [~]1-2 seconds before ripple onset, with the strongest modulation during awake ripples but minimal change during ripple-spindle coupling. These findings reveal state-dependent dynamics of LC-hippocampal interactions, positioning the LC as a key component of a cortical-subcortical network supporting systems-level memory consolidation.

neuroscience↗

Synchronous spiking associated with high gamma oscillations in prefrontal cortex exerts top-down control over a 5Hz-rhythmic modulation of spiking in locus coeruleus

The brainstem noradrenergic locus coeruleus (LC) is reciprocally connected with the prefrontal cortex (PFC). Strong coupling between LC spiking and depolarizing phase of slow (1 - 2 Hz) waves in the PFC field potentials during sleep and anesthesia suggests that the LC drives cortical state transition. Reciprocal LC-PFC connectivity should also allow interactions in the opposing (top-down) direction, but prior work has only studied prefrontal control over LC activity using direct electrical (or optogenetic) stimulation paradigms. Here, we describe the physiological characteristics of naturally occurring top-down prefrontal-coerulear interactions. Specifically, we recorded LC multi-unit activity (MUA) simultaneously with PFC single unit and local field potential (LFP) activity in urethane-anesthetized rats. We observed cross-regional coupling between the phase of ~5 Hz oscillations in LC population spike rate and the power of PFC LFP oscillations within the high Gamma (hGamma) range (60 - 200 Hz). Specifically, transient increases in PFC hGamma power preceded peaks in the ~5 Hz LC-MUA oscillation. Analysis of cross-regional transfer entropy demonstrated that the PFC hGamma transients were predictive of a transient increase in LC-MUA. A ~29 msec delay between these signals was consistent with the conduction velocity from the PFC to the LC. Finally, we showed that PFC hGamma transients are associated with synchronized spiking of a subset (27%) of PFC single units. Our data suggest that, PFC hGamma transients may indicate the timing of the top-down excitatory input to LC, at least under conditions when LC neuronal population activity fluctuates rhythmically at ~5 Hz. Synchronized PFC neuronal spiking that occurs during hGamma transients may provide a previously unknown mode of top-down control over the LC.

neuroscience↗

Monitoring large populations of locus coeruleus neurons reveals the non-global nature of the norepinephrine neuromodulatory system

Understanding the forebrain neuromodulation by the noradrenergic locus coeruleus (LC) is fundamental for cognitive and systems neuroscience. The diffuse projections of individual LC neurons and presumably their synchronous spiking have long been perceived as features of the global nature of noradrenergic neuromodulation. Yet, the commonly referenced \"synchrony\" underlying global neuromodulation, has never been assessed in a large population, nor has it been related to projection target specificity. Here, we recorded up to 52 single units simultaneously (3164 unit pairs in total) in rat LC and characterized projections by stimulating 15 forebrain sites. Spike count correlations were low and, surprisingly, only 13% of pairwise spike trains had synchronized spontaneous discharge. Notably, even noxious sensory stimulation did not activate the entire population, only evoking synchronized responses in ~16% of units on each trial. We also identified novel infra-slow (0.01-1 Hz) fluctuations of LC unit spiking that were asynchronous across the population. A minority, synchronized possibly by gap junctions, was biased toward restricted (non-global) forebrain projection patterns. Finally, we characterized two types of LC single units differing by waveform shape, propensity for synchronization, and interactions with cortex. These cell types formed finely-structured ensembles. Our findings suggest that the LC conveys a highly complex, differentiated, and potentially target-specific neuromodulatory signal.

neuroscience↗