Theta oscillation is considered a temporal scaffold for hippocampal computations that organizes the activity of spatially tuned cells known as place cells. Late phases of theta support prospective spatial representation via phase 'precession'. In contrast, some studies have hypothesized that early phases of theta may subserve both retrospective spatial representation via phase 'procession' and the encoding of new associations. Here, combining virtual reality, electrophysiology and computational modeling, we provide experimental evidence for such a functionally multiplexed phase code and describe how distinct spatial inputs control its manifestation. Specifically, when rats continuously learned new associations between external landmark (allothetic) cues and self-motion (idiothetic) cues, phase 'precession' remained intact, allowing continuous prediction of future positions. Conversely, phase 'procession' was diminished, matching the putative role in encoding at the early theta phase. This multiplexed phase code may serve as a general circuit logic for alternating different computations at a sub-second scale.

The lateral prefrontal cortex (LPFC) serves as a critical hub for higher-order cognitive and executive functions in the human brain, coordinating brain networks whose disruption has been implicated in many neurological and psychiatric disorders. While transcranial brain stimulation treatments often target the LPFC, our current understanding of connectivity profiles guiding these interventions based on electrophysiology remains limited. Here, we present a high-resolution probabilistic map of bidirectional effective connectivity between the LPFC and widespread cortical and subcortical regions. This map is derived from intracranial evoked potential analysis of 48,797 intracranial direct electrical stimulation runs across 759 implantations in 724 patients with refractory epilepsy (368 male, 354 female, two unspecified; mean age 24±13.5 years). We mapped probabilistic connectivity between brain parcels with adaptive resolution - higher resolution in the LPFC in the hemisphere of interest and lower elsewhere - maintaining statistical power while achieving 95% average confidence interval of ∼0.03 for connectivity probability estimates. In addition, the significance threshold (p-value) for probabilistic connectivity was obtained from surrogate distributions. Overall, we observed remarkable symmetry between afferent and efferent connectivity patterns of the LPFC, with a slight preference for efferent connections (mean slope = 0.92±0.09, mean R² = 0.93±0.025). For example, connections between the inferior frontal gyrus (IFG) and anterior cingulate showed notable directional asymmetry. The IFG strongly projected to most brain networks compared to other LPFC regions, with the strongest connectivity to the ventral attention network (0.26±0.01 compared to values between 0.15 and 0.21 in other LPFC regions). Posterior DLPFC demonstrated stronger connectivity to brain networks compared to anterior DLPFC regions (eg. 0.21±0.01 vs 0.15±0.01 for connectivity to ventral attention network), with the exception of the limbic cortex. All LPFC subregions strongly projected to the fronto-parietal (greater than 0.17) and ventral attention (greater than 0.15) networks, with moderate connections to the default network (between 0.1 and 0.15, with the maximum corresponding to superior DLPFC). Finally, latency analysis suggested that the left LPFC's influence on ipsilateral emotion-related regions is primarily polysynaptic, with particularly strong pathways from IFG to amygdala (0.16±0.02) and hippocampus (0.12±0.01). Taken together, these comprehensive connectivity maps provide a new detailed electrophysiological foundation for understanding the functional anatomy of LPFC and guiding targeted brain stimulation protocols.

Hippocampal place cells (PCs) are important for spatial coding and episodic memory. PCs' representations are modulated upon transitioning between environments (global remapping) but also change with repeated exposure to familiar spaces (representational drift). To gain insights into the mechanistic basis for this unique balance between circuit plasticity and stability, we used voltage imaging to longitudinally record the subthreshold and spiking activity of pyramidal neurons (PNs) and somatostatin-positive (SST) interneurons in CA1 during virtual navigation. A fraction of cells from both populations showed spatial representations, but many SSTs were speed-tuned or fired uniformly across space. Intracellular recordings revealed increased theta power and asymmetric ramp-like depolarization in PN place fields, while SSTs exhibited symmetric depolarization with no theta increase. Longitudinal recordings across weeks demonstrated representational drifts in both populations, although SSTs exhibited remarkably stable firing and subthreshold properties. Transition to a novel environment induced remapping in both populations, accompanied by increase in SST activity and reduction in PNs. These results provide new insights into how hippocampal circuits balance representational stability with experience-dependent plasticity.

Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.

Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.

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The precise structural and functional characteristics of input circuits targeting histaminergic neurons remain poorly understood. Here, using a rabies virus retrograde tracing system combined with fluorescence micro-optical sectioning tomography, we construct a 3D monosynaptic long-range input atlas of male mouse histaminergic neurons. We identify that the hypothalamus, thalamus, pallidum, and hippocampus constitute major input sources, exhibiting diverse spatial distribution patterns and neuronal type ratios. Notably, a specific layer distribution pattern and co-projection structures of upstream cortical neurons are well reconstructed at single-cell resolution. As histaminergic system is classically involved in sleep-wake regulation, we demonstrate that the lateral septum (predominantly supplying inhibitory inputs) and the paraventricular nucleus of the thalamus (predominantly supplying excitatory inputs) establish monosynaptic connections, exhibiting distinct functional dynamics and regulatory roles in rapid-eye-movement sleep. Collectively, our study provides a precise long-range input map of mouse histaminergic neurons at mesoscopic scale, laying a solid foundation for future systematic study of histaminergic neural circuits.

Nonpharmaceutical approaches based on gamma entrainment using sensory stimuli (GENUS) have shown promise in reducing Alzheimer's disease pathology in mouse models. While human studies remain limited, GENUS has been shown to alleviate aspects of neurodegeneration in patients with Alzheimer's disease. In this study, we analyze intracranial EEG data from 490 contacts across eleven patients with refractory epilepsy in response to three visual stimulation conditions. We find that 40 Hz visual stimulation successfully entrains neural activity beyond early visual areas, including the hippocampus and other cortical regions such as the temporal and frontal lobes. Additionally, we show that synchronization increases between the hippocampus and other cortical areas in response to the 40 Hz visual stimulation. Furthermore, combining stimulation with a simple visual oddball task alters the direction of information flow from frontal regions to the hippocampus and enhances both the strength and spatial extent of neural entrainment. These findings highlight the potential influence of cognitive engagement during sensory gamma stimulation and provide additional insights into the neurophysiological effects of 40 Hz visual stimulation.

Working memory allows us to keep information in memory for the time needed to perform a given task. Such fundamental cognitive ability relies on a neural circuit, including the retrosplenial cortex (RSC), connected to several cortical areas, functionally and anatomically, namely primary visual areas, and higher cognitive areas such as the cingulate, midcingulate, and subicular cortices. RSC bears intimate anatomical and functional connections with the hippocampus and has been implicated in integrating and translating spatial-temporal contextual information between ego- and allocentric reference frames to compute predictions about goals in goal-directed behaviors. The relative contribution of the hippocampus and retrosplenial cortex in working memory-guided behaviors remains unclear due to the lack of studies reversibly interfering with synapses connecting the two regions during such behaviors. We here used eArch3.0, a hyperpolarizing proton pump, to silence hippocampal axon terminals in RSC while animals perform a standard delayed non-match to place task. We found that such manipulation impairs memory retrieval, significantly decreasing performance and hastening decision-making. Furthermore, we found that such impairment outlasts light activation of the opsin, its effects being noticed up to three subsequent trials.