Inhibition mediated by group III metabotropic glutamate receptors regulates habenula activity and defensive behaviors.

Inhibition plays a key role in brain functions. While typically linked to GABA, inhibition can be induced by glutamate via metabotropic glutamate receptors (mGluRs). Here, we investigated the role of mGluR-mediated inhibition in the habenula, a conserved, glutamatergic brain hub involved in adaptive and defensive behaviors.

Calcium dynamics in habenular astrocytes regulate active coping within behavioral transitions.

Behavioral challenges prompt alternating vigorous and reduced mobility - active, passive coping - that optimize energy investment. Here, we show that disrupting astrocytes calcium signaling in the mouse lateral habenula (LHb) prolongs active coping. This state manifests through calcium elevations in both mouse and zebrafish habenular astrocytes.

Neuronal endolysosomal alterations induced by Apolipoprotein E4 emerge over time in primary neurons.

Apolipoprotein E4 (ApoE4), the major genetic risk factor for Alzheimer's disease (AD), is vital for understanding cellular processes involved in AD pathogenesis. Evidence implicates endosomes as a central player in AD, where endosomal enlargement in neurons is among the earliest changes in AD. This enlargement was reported to be enhanced in APOE4 carriers.

Single neurons and networks in the mouse claustrum integrate input from widespread cortical sources.

The claustrum is thought to be one of the most highly interconnected forebrain structures, but its organizing principles have yet to be fully explored at the level of single neurons. Here, we investigated the identity, connectivity, and activity of identified claustrum neurons in to understand how the structure's unique convergence of input and divergence of output support binding information streams. We found that neurons in the claustrum communicate with each other across efferent projection-defined modules which were differentially innervated by sensory and frontal cortical areas.

Direct entorhinal control of CA1 temporal coding.

Theta sequences of hippocampal activity supports planning and prediction, and in CA1 they are shaped by CA3 and entorhinal (layer III) inputs. We targeted entorhinal inputs with highly specific optogenetic inhibition, leaving the remaining circuit intact. While CA1 spatial coding properties were largely unaffected, the slope and range of theta phase precession were impaired.

Age-Related Increase in Locus Ceruleus Activity and Connectivity with the Prefrontal Cortex during Ambiguity Processing.

Interpreting ambiguous environmental cues, like facial expressions, becomes increasingly challenging with age, especially as cognitive resources decline. Managing these challenges requires adaptive neural mechanisms that are essential for maintaining mental well-being. The locus ceruleus (LC), the brain's main norepinephrine source, regulates attention, arousal, and stress response.

Event structure sculpts neural population dynamics in the lateral entorhinal cortex.

Our experience of the world is a continuous stream of events that must be segmented and organized at multiple timescales. The neural mechanisms underlying this process remain unknown. In this work, we simultaneously recorded hundreds to thousands of neurons in the lateral entorhinal cortex of freely behaving rats.

Impact of symmetry in local learning rules on predictive neural representations and generalization in spatial navigation.

In spatial cognition, the Successor Representation (SR) from reinforcement learning provides a compelling candidate of how predictive representations are used to encode space. In particular, hippocampal place cells are hypothesized to encode the SR. Here, we investigate how varying the temporal symmetry in learning rules influences those representations.

Pathological biomarkers for Alzheimer's disease in cognitively unimpaired individuals are not associated with cognitive decline at two-year follow-up.

Background: Alzheimer's disease (AD) pathology may be present in cognitively unimpaired individuals, but the clinical implications of this are unclear. Subtle cognitive decline is a potential marker of preclinical AD.

Objective: To investigate whether two-year cognitive change scores are influenced by AD-linked cerebrospinal fluid (Aβ p-tau, t-tau, NfL) or plasma (p217, BD-tau, NfL) biomarker pathology in individuals who are cognitively unimpaired at baseline.

Hippocampal-entorhinal cognitive maps and cortical motor system represent action plans and their outcomes.

Efficiently interacting with the environment requires weighing and selecting among multiple alternative actions based on their associated outcomes. However, the neural mechanisms underlying these processes are still debated. We show that forming relations between arbitrary action-outcome associations involve building a cognitive map.

Dorsal-Caudal and Ventral Hippocampi Target Different Cell Populations in the Medial Frontal Cortex in Rodents.

Direct projections from the ventral hippocampus (vHPC) to the medial frontal cortex (MFC) play crucial roles in memory and emotional regulation. Using anterograde transsynaptic tracing and ex vivo electrophysiology in male mice, we document a previously unexplored pathway that parallels the established vHPC-MFC connectivity. This pathway connects the dorsal-caudal hippocampus (dcHPC) to specific subregions of the ventral MFC (vMFC), in particular the dorsal peduncular cortex.

Hippocampus shapes entorhinal cortical output through a direct feedback circuit.

Our brains integrate sensory, cognitive and internal state information with memories to extract behavioral relevance. Cortico-hippocampal interactions likely mediate this interplay, but underlying circuit mechanisms remain elusive. Unlike the entorhinal cortex-to-hippocampus pathway, we know little about the organization and function of the hippocampus-to-cortex feedback circuit.

Exploring the role of dimensionality transformation in episodic memory.

Episodic memory must accomplish two adversarial goals: encoding and storing a multitude of experiences without exceeding the finite neuronal structure of the brain, and recalling memories in vivid detail. Dimensionality reduction and expansion ('dimensionality transformation') enable the brain to meet these demands. Reduction compresses sensory input into simplified, storable codes, while expansion reconstructs vivid details.

Similar neural networks for anger and pride in older adults.

There has been a significant amount of research on the neural mechanisms underlying "basic emotions" but relatively less research on complex social emotions like pride, embarrassment, guilt, or shame. The aim of this study was to investigate age-related differences in the neural basis of processing anger, joy, pride, and embarrassment, and possible association with well-being measurements, such as depression, anxiety and stress. Twenty-four younger and twenty-five older adults underwent functional imaging while viewing videos of four emotions and indicating the emotion expressed.

Left-right-alternating theta sweeps in entorhinal-hippocampal maps of space.

Place cells in the hippocampus and grid cells in the entorhinal cortex are elements of a neural map of self position. For these cells to benefit navigation, their representation must be dynamically related to the surrounding locations. A candidate mechanism for linking places along an animal's path has been described for place cells, in which the sequence of spikes in each cycle of the hippocampal theta oscillation encodes a trajectory from the animal's current location towards upcoming locations.

Hippocampal coding of identity, sex, hierarchy, and affiliation in a social group of wild fruit bats.

Social animals live in groups and interact volitionally in complex ways. However, little is known about neural responses under such natural conditions. Here, we investigated hippocampal CA1 neurons in a mixed-sex group of five to 10 freely behaving wild Egyptian fruit bats that lived continuously in a laboratory-based cave and formed a stable social network.

The role of oscillations in grid cells' toroidal topology.

Persistent homology applied to the activity of grid cells in the Medial Entorhinal Cortex suggests that this activity lies on a toroidal manifold. By analyzing real data and a simple model, we show that neural oscillations play a key role in the appearance of this toroidal topology. To quantitatively monitor how changes in spike trains influence the topology of the data, we first define a robust measure for the degree of toroidality of a dataset.

Motile cilia modulate neuronal and astroglial activity in the zebrafish larval brain.

The brain uses a specialized system to transport cerebrospinal fluid (CSF), consisting of interconnected ventricles lined by motile ciliated ependymal cells. These cells act jointly with CSF secretion and cardiac pressure gradients to regulate CSF dynamics. To date, the link between cilia-mediated CSF flow and brain function is poorly understood.

Intraneuronal binding of amyloid beta with reelin-Implications for the onset of Alzheimer's disease.

Numerous studies of the human brain supported by experimental results from rodent and cell models point to a central role for intracellular amyloid beta (Aβ) in the onset of Alzheimer's disease (AD). In a rat model used to study AD, it was recently shown that in layer II neurons of the anteriolateral entorhinal cortex expressing high levels of the glycoprotein reelin (Re+alECLII neurons), reelin and Aβ engage in a direct protein-protein interaction. If reelin functions as a sink for intracellular Aβ and if the binding to reelin makes Aβ physiologically inert, it implies that reelin can prevent the neuron from being exposed to the harmful effects typically associated with increased levels of oligomeric Aβ.

Cyto-, gene, and multireceptor architecture of the early postnatal mouse hippocampal complex.

Neurotransmitter receptors are key molecules in signal transmission in the adult brain, and their precise spatial and temporal balance expressions also play a critical role in normal brain development. However, the specific balance expression of multiple receptors during hippocampal development is not well characterized. In this study, we used quantitative in vivo receptor autoradiography to measure the distributions and densities of 18 neurotransmitter receptor types in the mouse hippocampal complex at postnatal day 7, and compared them with the expressions of their corresponding encoding genes.

Evidence for convergence of distributed cortical processing in band-like functional zones in human entorhinal cortex.

The wide array of cognitive functions associated with the hippocampus is supported through interactions with the cerebral cortex. However, most of the direct cortical input to the hippocampus originates in the entorhinal cortex, forming the hippocampal-entorhinal system. In humans, the role of the entorhinal cortex in mediating hippocampal-cortical interactions remains unknown.

Reverse engineering of feedforward cortical-Hippocampal microcircuits for modelling neural network function and dysfunction.

Engineered biological neural networks are indispensable models for investigation of neural function and dysfunction from the subcellular to the network level. Notably, advanced neuroengineering approaches are of significant interest for their potential to replicate the topological and functional organization of brain networks. In this study, we reverse engineered feedforward neural networks of primary cortical and hippocampal neurons, using a custom-designed multinodal microfluidic device with Tesla valve inspired microtunnels.