Measuring synaptic efficacy and defining the rules for induction of synaptic plasticity at identified connections in the mammalian brain is essential for understanding how synapses contribute to learning and memory. This requires new approaches to selectively evoke presynaptic activity and measure postsynaptic responses with high spatiotemporal resolution and high sensitivity over long periods in vivo. Here we develop an all-optical approach to probe synaptic plasticity at identified cerebellar synapses in awake, behaving mice. We developed and applied JEDI-2Psub, a genetically encoded voltage indicator with increased sensitivity around resting membrane potentials, to record subthreshold and suprathreshold activity in Purkinje cell (PC) dendrites while selectively activating their granule cell (GrC) inputs using optogenetics and their climbing fiber (CF) inputs using sensory stimulation. We measured synaptic potentials and complex spike signals across the dendrites of multiple neighboring PCs, enabling us to examine correlations in voltage signals within and between neurons. We show how pairing GrC activity with sensory-evoked CF inputs can trigger long-term plasticity of inhibitory responses in PCs. These results provide a blueprint for defining the rules for plasticity induction at identified synapses in awake animals during behavior.

Every explored environment is represented in the hippocampus by the activity of distinct populations of pyramidal cells (PCs) that typically fire at specific locations called their place fields (PFs). New PFs are constantly born even in familiar surroundings (during representational drift), and many rapidly emerge when the animal explores a new or altered environment (during global or partial remapping). Behavioral time scale synaptic plasticity (BTSP), a plasticity mechanism based on prolonged somatic action potential (AP) bursts induced by dendritic Ca/NMDA plateau potentials, was recently proposed as the main cellular mechanism underlying new PF formations (PFFs), but it is unclear whether burst-associated large somatic [Ca] transients are always necessary and/or sufficient for PFF. To address this issue, here we performed in vivo two-photon [Ca] imaging of hippocampal CA1 PCs in head-restrained mice to investigate somatic [Ca] dynamics underlying PFFs in familiar and novel virtual environments. Our results demonstrate that although many PFs are formed by BTSP-like events, PFs also emerge with initial [Ca] dynamics that do not match any of the characteristics of BTSP. BTSP- and non-BTSP-like new PFFs occur spontaneously in familiar environments, during neuronal representational switches, and instantaneously in new environments. Our data also reveal that solitary [Ca] transients with larger amplitudes than those evoking BTSP-like PFFs frequently occur without inducing PFs, demonstrating that large [Ca] transients per se are not sufficient for PFF.

Episodic memories are initially encoded in the hippocampus and subsequently undergo systems consolidation into the neocortex. The nature of memories stored in the hippocampus and neocortex differs, with the cortex encoding memories in more generalized forms. Although several brain regions encode social information, the specific cortical regions and circuits involved in the consolidation of social memories and the nature of the information encoded in the cortex remain unclear. Using in vivo Ca imaging and optogenetic manipulations, we found that infralimbic (IL) neurons projecting to the nucleus accumbens shell (IL) store consolidated social memories in male mice. Inactivating IL neurons that responded to a familiar conspecific impaired the recognition of other familiar mice including littermates, demonstrating that these neuronal activities support social familiarity. Furthermore, inactivating hippocampal ventral CA1 neurons projecting to the IL region disrupted the consolidation of memory for newly familiarized mice while sparing the recognition of littermates. These findings demonstrate the critical role of hippocampal-cortical interactions in the consolidation of social memory.

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.

Basal Ganglia Advances is a collection highlighting research on the structure, function, and disorders of the basal ganglia. It features studies spanning neuroscience, clinical insights, and computational models, serving as a hub for advances in movement, cognition, and behavior.

This perspective highlights new work suggesting the need for revision of the canonical direct-indirect model of the basal ganglia's influence on movement, with fresh evidence that there is a formerly unappreciated pair of direct and indirect pathways that parallel the standard model's canonical direct and indirect pathways, and promising evidence pointing toward improved clinical treatments for Parkinson's disease. As a working hypothesis, it is suggested that the non-canonical direct and indirect pathways, which arise in striosomes, might act as homeostatic circuits that can reign in or amplify the activity of the canonical pathways in the face of their imbalance, including that occurring in hyperkinetic or hypokinetic disorders. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.