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Nature Communications May 2024The role of the hippocampus in spatial navigation has been primarily studied in nocturnal mammals, such as rats, that lack many adaptations for daylight vision. Here we...
The role of the hippocampus in spatial navigation has been primarily studied in nocturnal mammals, such as rats, that lack many adaptations for daylight vision. Here we demonstrate that during 3D navigation, the common marmoset, a new world primate adapted to daylight, predominantly uses rapid head-gaze shifts for visual exploration while remaining stationary. During active locomotion marmosets stabilize the head, in contrast to rats that use low-velocity head movements to scan the environment as they locomote. Pyramidal neurons in the marmoset hippocampus CA3/CA1 regions predominantly show mixed selectivity for 3D spatial view, head direction, and place. Exclusive place selectivity is scarce. Inhibitory interneurons are predominantly mixed selective for angular head velocity and translation speed. Finally, we found theta phase resetting of local field potential oscillations triggered by head-gaze shifts. Our findings indicate that marmosets adapted to their daylight ecological niche by modifying exploration/navigation strategies and their corresponding hippocampal specializations.
Topics: Animals; Callithrix; Spatial Navigation; Hippocampus; Male; Locomotion; Vision, Ocular; Pyramidal Cells; Head Movements; Interneurons; Female; Behavior, Animal; CA1 Region, Hippocampal
PubMed: 38744848
DOI: 10.1038/s41467-024-48374-2 -
Science Advances May 2024During cerebral cortex development, excitatory pyramidal neurons (PNs) establish specific projection patterns while receiving inputs from GABAergic inhibitory...
During cerebral cortex development, excitatory pyramidal neurons (PNs) establish specific projection patterns while receiving inputs from GABAergic inhibitory interneurons (INs). Whether these inhibitory inputs can shape PNs' projection patterns is, however, unknown. While layer 4 (L4) PNs of the primary somatosensory (S1) cortex are all born as long-range callosal projection neurons (CPNs), most of them acquire local connectivity upon activity-dependent elimination of their interhemispheric axons during postnatal development. Here, we demonstrate that precise developmental regulation of inhibition is key for the retraction of S1L4 PNs' callosal projections. Ablation of somatostatin INs leads to premature inhibition from parvalbumin INs onto S1L4 PNs and prevents them from acquiring their barrel-restricted local connectivity pattern. As a result, adult S1L4 PNs retain interhemispheric projections responding to tactile stimuli, and the mice lose whisker-based texture discrimination. Overall, we show that temporally ordered IN activity during development is key to shaping local ipsilateral S1L4 PNs' projection pattern, which is required for fine somatosensory processing.
Topics: Animals; Interneurons; GABAergic Neurons; Somatosensory Cortex; Mice; Pyramidal Cells; Parvalbumins
PubMed: 38728406
DOI: 10.1126/sciadv.adj9911 -
Heliyon May 2024We have recently shown delayed increases in GABA receptor (GABAR) subunit protein levels in the hippocampal dentate gyrus (DG), but not in the pyramidal CA1 and CA3...
We have recently shown delayed increases in GABA receptor (GABAR) subunit protein levels in the hippocampal dentate gyrus (DG), but not in the pyramidal CA1 and CA3 regions, at 15-30 days after the systemic single administration of trimethyltin (TMT) in mice. An attempt was thus made to determine whether the delayed increases return to the control levels found in naive mice afterward. In the DG on hippocampal slices obtained at 90 days after the administration, however, marked increases were still seen in protein levels of both GABAR1 and GABAR2 subunits without significant changes in calbindin and glial fibrillary acidic protein (GFAP) levels on immunoblotting analysis. Fluoro-Jade B staining clearly revealed the absence of degenerated neurons from the DG at 90 days after the administration. Although co-localization was invariably detected between GABAR2 subunit and GFAP in the DG at 30 days on immunohistochemical analysis, GABAR2-positive cells did not merge well with GFAP-positive cells in the DG at 90 days. These results suggest that both GABAR1 and GABAR2 subunits would be tardily and sustainably up-regulated by cells other than neurons and astrocytes in the murine DG at 90 days after a systemic single injection of TMT.
PubMed: 38720739
DOI: 10.1016/j.heliyon.2024.e29713 -
Aging Cell May 2024Behavioral changes or neuropsychiatric symptoms (NPSs) are common features in dementia and are associated with accelerated cognitive impairment and earlier deaths....
Behavioral changes or neuropsychiatric symptoms (NPSs) are common features in dementia and are associated with accelerated cognitive impairment and earlier deaths. However, how NPSs are intertwined with cognitive decline remains elusive. In this study, we identify that the basolateral amygdala (BLA) is a key brain region that is associated with mood disorders and memory decline in the AD course. During the process from pre- to post-onset in AD, the dysfunction of parvalbumin (PV) interneurons and pyramidal neurons in the amygdala leads to hyperactivity of pyramidal neurons in the basal state and insensitivity to external stimuli. We further demonstrate that serotonin (5-HT) receptors in distinct neurons synergistically regulate the BLA microcircuit of AD rather than 5-HT levels, in which both restrained inhibitory inputs by excessive 5-HTR signaling in PV interneurons and depolarized pyramidal neurons via upregulated 5-HTR contribute to aberrant neuronal hyperactivity. Downregulation of these two 5-HT receptors simultaneously enables neurons to resist β-amyloid peptides (Aβ) neurotoxicity and ameliorates the mood and cognitive defects. Therefore, our study reveals a crucial role of 5-HT receptors for regulating neuronal homeostasis in AD pathogenesis, and this would provide early intervention and potential targets for AD cognitive decline.
PubMed: 38716507
DOI: 10.1111/acel.14187 -
Frontiers in Cellular Neuroscience 2024The balance between excitation and inhibition is essential to the proper function of cortical circuits. To maintain this balance during dynamic network activity,...
The balance between excitation and inhibition is essential to the proper function of cortical circuits. To maintain this balance during dynamic network activity, modulation of the strength of inhibitory synapses is a central requirement. In this study, we aimed to characterize perisomatic inhibition and its plasticity onto pyramidal cells (PCs) in the subiculum, the main output region of the hippocampus. We performed whole-cell patch-clamp recordings from the two main functional PC types, burst (BS) and regular spiking (RS) neurons in acute rat hippocampal slices and applied two different extracellular high-frequency stimulation paradigms: non-associative (presynaptic stimulation only) and associative stimulation (concurrent pre-and postsynaptic stimulation) to induce plasticity. Our results revealed cell type-specific differences in the expression of inhibitory plasticity depending on the induction paradigm: While associative stimulation caused robust inhibitory plasticity in both cell types, non-associative stimulation produced long-term potentiation in RS, but not in BS PCs. Analysis of paired-pulse ratio, variance of IPSPs, and postsynaptic Ca2+ buffering indicated a dominant postsynaptic calcium-dependent signaling and expression of inhibitory plasticity in both PC types. This divergence in inhibitory plasticity complements a stronger inhibition and a higher intrinsic excitability in RS as compared to BS neurons, suggesting differential involvement of the two PC types during network activation and information processing in the subiculum.
PubMed: 38716238
DOI: 10.3389/fncel.2024.1368627 -
PLoS Biology May 2024Synaptic adhesion molecules (SAMs) are evolutionarily conserved proteins that play an important role in the form and function of neuronal synapses. Teneurins (Tenms) and...
Synaptic adhesion molecules (SAMs) are evolutionarily conserved proteins that play an important role in the form and function of neuronal synapses. Teneurins (Tenms) and latrophilins (Lphns) are well-known cell adhesion molecules that form a transsynaptic complex. Recent studies suggest that Tenm3 and Lphn2 (gene symbol Adgrl2) are involved in hippocampal circuit assembly via their topographical expression. However, it is not known whether other teneurins and latrophilins display similar topographically restricted expression patterns during embryonic and postnatal development. Here, we reveal the cartography of all teneurin (Tenm1-4) and latrophilin (Lphn1-3 [Adgrl1-3]) paralog expression in the mouse hippocampus across prenatal and postnatal development as monitored by large-scale single-molecule RNA in situ hybridization mapping. Our results identify a striking heterogeneity in teneurin and latrophilin expression along the spatiotemporal axis of the hippocampus. Tenm2 and Tenm4 expression levels peak at the neonatal stage when compared to Tenm1 and Tenm3, while Tenm1 expression is restricted to the postnatal pyramidal cell layer. Tenm4 expression in the dentate gyrus (DG) exhibits an opposing topographical expression pattern in the embryonic and neonatal hippocampus. Our findings were validated by analyses of multiple RNA-seq datasets at bulk, single-cell, and spatial levels. Thus, our study presents a comprehensive spatiotemporal map of Tenm and Lphn expression in the hippocampus, showcasing their diverse expression patterns across developmental stages in distinct spatial axes.
Topics: Animals; Hippocampus; Mice; Nerve Tissue Proteins; Receptors, Peptide; Gene Expression Regulation, Developmental; Female; Mice, Inbred C57BL; Male; Tenascin; Receptors, G-Protein-Coupled
PubMed: 38713721
DOI: 10.1371/journal.pbio.3002599 -
Brain Communications 2024Synapse loss is currently the best biological correlate of cognitive decline in Alzheimer's disease and other tauopathies. Synapses seem to be highly vulnerable to...
Synapse loss is currently the best biological correlate of cognitive decline in Alzheimer's disease and other tauopathies. Synapses seem to be highly vulnerable to tau-mediated disruption in neurodegenerative tauopathies. However, it is unclear how and when this leads to alterations in function related to the progression of tauopathy and neurodegeneration. We used the well-characterized rTg4510 mouse model of tauopathy at 5-6 months and 7-8 months of age, respectively, to study the functional impact of cortical synapse loss. The earlier age was used as a model of prodromal tauopathy, with the later age corresponding to more advanced tau pathology and presumed progression of neurodegeneration. Analysis of synaptic protein expression in the somatosensory cortex showed significant reductions in synaptic proteins and NMDA and AMPA receptor subunit expression in rTg4510 mice. Surprisingly, whole-cell patch clamp electrophysiology from putative pyramidal neurons in layer 2/3 of the somatosensory cortex suggested no functional alterations in layer 4 to layer 2/3 synaptic transmission at 5-6 months. From these same neurons, however, there were alterations in dendritic structure, with increased branching proximal to the soma in rTg4510 neurons. Therefore, whole-cell patch clamp recordings were utilized to investigate synaptic function and integration in putative pyramidal neurons in layer 2/3 of the somatosensory cortex. These recordings revealed a significant increase in the peak response to synaptically driven sensory stimulation-evoked activity and a loss of temporal fidelity of the evoked signal to the input stimulus in rTg4510 neurons. Together, these data suggest that loss of synapses, changes in receptor expression and dendritic restructuring may lead to alterations in synaptic integration at a network level. Understanding these compensatory processes could identify targets to help delay symptomatic onset of dementia.
PubMed: 38712321
DOI: 10.1093/braincomms/fcae134 -
Current Biology : CB May 2024The hippocampal formation contains neurons responsive to an animal's current location and orientation, which together provide the organism with a neural map of space....
The hippocampal formation contains neurons responsive to an animal's current location and orientation, which together provide the organism with a neural map of space. Spatially tuned neurons rely on external landmark cues and internally generated movement information to estimate position. An important class of landmark cue are the boundaries delimiting an environment, which can define place cell field position and stabilize grid cell firing. However, the precise nature of the sensory information used to detect boundaries remains unknown. We used 2-dimensional virtual reality (VR) to show that visual cues from elevated walls surrounding the environment are both sufficient and necessary to stabilize place and grid cell responses in VR, when only visual and self-motion cues are available. By contrast, flat boundaries formed by the edges of a textured floor did not stabilize place and grid cells, indicating only specific forms of visual boundary stabilize hippocampal spatial firing. Unstable grid cells retain internally coherent, hexagonally arranged firing fields, but these fields "drift" with respect to the virtual environment over periods >5 s. Optic flow from a virtual floor does not slow drift dynamics, emphasizing the importance of boundary-related visual information. Surprisingly, place fields are more stable close to boundaries even with floor and wall cues removed, suggesting invisible boundaries are inferred using the motion of a discrete, separate cue (a beacon signaling reward location). Subsets of place cells show allocentric directional tuning toward the beacon, with strength of tuning correlating with place field stability when boundaries are removed.
Topics: Virtual Reality; Cues; Animals; Grid Cells; Male; Hippocampus; Space Perception; Rats; Place Cells; Visual Perception; Rats, Long-Evans; Orientation
PubMed: 38701787
DOI: 10.1016/j.cub.2024.04.026 -
Scientific Reports May 2024β-Thalassaemia is one of the most common genetic diseases worldwide. During the past few decades, life expectancy of patients has increased significantly owing to...
β-Thalassaemia is one of the most common genetic diseases worldwide. During the past few decades, life expectancy of patients has increased significantly owing to advance in medical treatments. Cognitive impairment, once has been neglected, has gradually become more documented. Cognitive impairment in β-thalassaemia patients is associated with natural history of the disease and socioeconomic factors. Herein, to determined effect of β-thalassaemia intrinsic factors, 22-month-old β-thalassaemia mouse was used as a model to assess cognitive impairment and to investigate any aberrant brain pathology in β-thalassaemia. Open field test showed that β-thalassaemia mice had decreased motor function. However, no difference of neuronal degeneration in primary motor cortex, layer 2/3 area was found. Interestingly, impaired learning and memory function accessed by a Morris water maze test was observed and correlated with a reduced number of living pyramidal neurons in hippocampus at the CA3 region in β-thalassaemia mice. Cognitive impairment in β-thalassaemia mice was significantly correlated with several intrinsic β-thalassaemic factors including iron overload, anaemia, damaged red blood cells (RBCs), phosphatidylserine (PS)-exposed RBC large extracellular vesicles (EVs) and PS-exposed medium EVs. This highlights the importance of blood transfusion and iron chelation in β-thalassaemia patients. In addition, to improve patients' quality of life, assessment of cognitive functions should become part of routine follow-up.
Topics: Animals; beta-Thalassemia; Cognitive Dysfunction; Mice; Hippocampus; Disease Models, Animal; Male; Neurons; Iron Overload; Extracellular Vesicles; Erythrocytes; Pyramidal Cells; Maze Learning
PubMed: 38698053
DOI: 10.1038/s41598-024-60459-y -
Nature Communications May 2024Hippocampal place cells represent the position of a rodent within an environment. In addition, recent experiments show that the CA1 subfield of a passive observer also...
Hippocampal place cells represent the position of a rodent within an environment. In addition, recent experiments show that the CA1 subfield of a passive observer also represents the position of a conspecific performing a spatial task. However, whether this representation is allocentric, egocentric or mixed is less clear. In this study we investigated the representation of others during free behavior and in a task where female mice learned to follow a conspecific for a reward. We found that most cells represent the position of others relative to self-position (social-vector cells) rather than to the environment, with a prevalence of purely egocentric coding modulated by context and mouse identity. Learning of a pursuit task improved the tuning of social-vector cells, but their number remained invariant. Collectively, our results suggest that the hippocampus flexibly codes the position of others in multiple coordinate systems, albeit favoring the self as a reference point.
Topics: Animals; Female; CA1 Region, Hippocampal; Mice; Mice, Inbred C57BL; Place Cells; Reward; Behavior, Animal
PubMed: 38697969
DOI: 10.1038/s41467-024-47453-8