Recent anatomical evidence suggests a functionally significant back-projection pathway from the subiculum to the CA1. Here we show that the afferent circuitry of CA1-projecting subicular neurons is ...biased by inputs from CA1 inhibitory neurons and the visual cortex, but lacks input from the entorhinal cortex. Efferents of the CA1-projecting subiculum neurons also target the perirhinal cortex, an area strongly implicated in object-place learning. We identify a critical role for CA1-projecting subicular neurons in object-location learning and memory, and show that this projection modulates place-specific activity of CA1 neurons and their responses to displaced objects. Together, these experiments reveal a novel pathway by which cortical inputs, particularly those from the visual cortex, reach the hippocampal output region CA1. Our findings also implicate this circuitry in the formation of complex spatial representations and learning of object-place associations.
Humans and other animals have a remarkable capacity to translate their position from one spatial frame of reference to another. The ability to seamlessly move between top-down and first-person views ...is important for navigation, memory formation, and other cognitive tasks. Evidence suggests that the medial temporal lobe and other cortical regions contribute to this function. To understand how a neural system might carry out these computations, we used variational autoencoders (VAEs) to reconstruct the first-person view from the top-down view of a robot simulation, and vice versa. Many latent variables in the VAEs had similar responses to those seen in neuron recordings, including location-specific activity, head direction tuning, and encoding of distance to local objects. Place-specific responses were prominent when reconstructing a first-person view from a top-down view, but head direction–specific responses were prominent when reconstructing a top-down view from a first-person view. In both cases, the model could recover from perturbations without retraining, but rather through remapping. These results could advance our understanding of how brain regions support viewpoint linkages and transformations.
The hippocampus and posterior parietal cortex are implicated in both episodic memory and encoding of position in an environment. In the present study, we examine the impact of locomotor behaviors ...associated with movement in both the horizontal and vertical dimensions on population activity patterns in these two brain structures. We utilized a five-looped, squared spiral track containing stair segments, ramp segments, and flat segments. In addition to encoding locations along the full route, posterior parietal cortex population activity demonstrates strong pattern recurrence for similar action types at different locations in the environment. Additionally, posterior parietal and hippocampal neurons exhibit parallel modulation in the scale of representation that follows behavioral dynamics required for track traversal. These findings build on prior work examining spatial mapping in the vertical dimension and provide a better understanding of how a series of actions and visited locations can be coordinated in the generation of episodic memory.
Alzheimer's disease (AD) causes progressive age-related defects in memory and cognitive function and has emerged as a major health and socio-economic concern in the US and worldwide. To develop ...effective therapeutic treatments for AD, we need to better understand the neural mechanisms by which AD causes memory loss and cognitive deficits. Here we examine large-scale hippocampal neural population calcium activities imaged at single cell resolution in a triple-transgenic Alzheimer's disease mouse model (3xTg-AD) that presents both amyloid plaque and neurofibrillary pathological features along with age-related behavioral defects. To measure encoding of environmental location in hippocampal neural ensembles in the 3xTg-AD mice in vivo, we performed GCaMP6-based calcium imaging using head-mounted, miniature fluorescent microscopes (“miniscopes”) on freely moving animals. We compared hippocampal CA1 excitatory neural ensemble activities during open-field exploration and track-based route-running behaviors in age-matched AD and control mice at young (3–6.5 months old) and old (18–21 months old) ages. During open-field exploration, 3xTg-AD CA1 excitatory cells display significantly higher calcium activity rates compared with Non-Tg controls for both the young and old age groups, suggesting that in vivo enhanced neuronal calcium ensemble activity is a disease feature. CA1 neuronal populations of 3xTg-AD mice show lower spatial information scores compared with control mice. The spatial firing of CA1 neurons of old 3xTg-AD mice also displays higher sparsity and spatial coherence, indicating less place specificity for spatial representation. We find locomotor speed significantly modulates the amplitude of hippocampal neural calcium ensemble activities to a greater extent in 3xTg-AD mice during open field exploration. Our data offer new and comprehensive information about age-dependent neural circuit activity changes in this important AD mouse model and provide strong evidence that spatial coding defects in the neuronal population activities are associated with AD pathology and AD-related memory behavioral deficits.
•Our study is the first to apply miniscope-based calcium imaging in freely behaving AD model mice.•Spatial coding defects are found in hippocampal neural calcium ensembles in AD mice.•AD mice show enhanced neuronal calcium activities in CA1 compared with controls.•CA1 neuronal populations of AD mice show lower spatial information score.•Locomotion modulates CA1 calcium activity amplitudes in AD mice.
Rats readily switch between foraging and more complex navigational behaviors such as pursuit of other rats or prey. These tasks require vastly different tracking of multiple behaviorally significant ...variables including self-motion state. To explore whether navigational context modulates self-motion tracking, we examined self-motion tuning in posterior parietal cortex neurons during foraging versus visual target pursuit. Animals performing the pursuit task demonstrate predictive processing of target trajectories by anticipating and intercepting them. Relative to foraging, pursuit yields multiplicative gain modulation of self-motion tuning and enhances self-motion state decoding. Self-motion sensitivity in parietal cortex neurons is, on average, history dependent regardless of behavioral context, but the temporal window of self-motion integration extends during target pursuit. Finally, many self-motion-sensitive neurons conjunctively track the visual target position relative to the animal. Thus, posterior parietal cortex functions to integrate the location of navigationally relevant target stimuli into an ongoing representation of past, present, and future locomotor trajectories.
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•Rats pursue moving visual targets and make predictions about their paths•Pursuit behavior enhances self-motion coding in parietal cortex via gain modulation•Pursuit increases timescale of instantaneous trajectory mappings in parietal cortex•Parietal cortex neurons conjunctively code self-motion and egocentric target position
Alexander et al. examine rats pursuing visual targets and characterize emergent predictive behaviors. Relative to free exploration, pursuit elicits enhanced coding of self-motion in the parietal cortex over extended temporal durations. A subset of parietal cortex neurons code for self-motion state and egocentric position of the pursuit target simultaneously.
A key challenge in developing diagnosis and treatments for Alzheimer's disease (AD) is to detect abnormal network activity at as early a stage as possible. To date, behavioral and neurophysiological ...investigations in AD model mice have yet to conduct a longitudinal assessment of cellular pathology, memory deficits, and neurophysiological correlates of neuronal activity. We therefore examined the temporal relationships between pathology, neuronal activities and spatial representation of environments, as well as object location memory deficits across multiple stages of development in the 5xFAD mice model and compared these results to those observed in wild-type mice. We performed longitudinal in vivo calcium imaging with miniscope on hippocampal CA1 neurons in behaving mice. We find that 5xFAD mice show amyloid plaque accumulation, depressed neuronal calcium activity during immobile states, and degenerate and unreliable hippocampal neuron spatial tuning to environmental location at early stages by 4 months of age while their object location memory (OLM) is comparable to WT mice. By 8 months of age, 5xFAD mice show deficits of OLM, which are accompanied by progressive degradation of spatial encoding and, eventually, impaired CA1 neural tuning to object-location pairings. Furthermore, depressed neuronal activity and unreliable spatial encoding at early stage are correlated with impaired performance in OLM at 8-month-old. Our results indicate the close connection between impaired hippocampal tuning to object-location and the presence of OLM deficits. The results also highlight that depressed baseline firing rates in hippocampal neurons during immobile states and unreliable spatial representation precede object memory deficits and predict memory deficits at older age, suggesting potential early opportunities for AD detecting.
•In vivo longitudinal miniscope calcium imaging was applied in freely behaving 5xFAD mice.•Depressed CA1 neuronal activity and spatial encoding deficits develop at early stage.•Impaired circuit function precedes object location memory deficit in 5xFAD mice.•Impaired circuit function at early stage predicts future memory deficits.
Fluid navigation requires constant updating of planned movements to adapt to evolving obstacles and goals. For that reason, a neural substrate for navigation demands spatial and environmental ...information and the ability to effect actions through efferents. The secondary motor cortex (M2) is a prime candidate for this role given its interconnectivity with association cortices that encode spatial relationships and its projection to the primary motor cortex. Here, we report that M2 neurons robustly encode both planned and current left/right turning actions across multiple turn locations in a multi-route navigational task. Comparisons within a common statistical framework reveal that M2 neurons differentiate contextual factors, including environmental position, route, action sequence, orientation, and choice availability. Despite significant modulation by environmental factors, action planning, and execution are the dominant output signals of M2 neurons. These results identify the M2 as a structure integrating spatial information toward the updating of planned movements.
•M2 ensembles discriminate the specific motor acts associated with navigation•Current and planned actions and their spatial context are encoded by M2 neurons•M2 activity represents decision-making context during navigation•Location, direction, and route progress all affect M2 action-encoding activity
Olson et al. examine the firing of secondary motor cortex neurons in the context of navigation. They demonstrate that this region exhibits activity dynamics consistent with integration of spatial and directional information toward the planning and execution of locomotor actions.
Navigation is often constrained to pathways, and a recurring problem concerns whether to turn left or right when approaching an intersection. We examined this problem during T-maze performance in ...which the maze location in the recording environment varied over five-trial blocks and analyzed the associated positional firing patterns of hippocampal CA1 and posterior parietal cortex neurons. An arbitrary partitioning of the environmental space determined the left versus right turning rule for T-maze behavior. Under these conditions, rats learned the logical fragmentation of allocentric space into left turn and right turn sub-regions. Paradoxically, under these conditions, the spatial tuning of both posterior parietal cortex and hippocampal CA1 neurons followed the frame of reference given by the T-maze, as opposed to the location in the environment. Moreover, first trials within each block were associated with distinct firing rate changes for both posterior parietal cortex and hippocampal CA1 neurons. These data support a model where spatial tuning by hippocampus and cortex can interact to guide choice behavior in complex, path-based environments where a correct turn choice varies across environmental locations, and as a function of recent experience.
Similarities and differences in the visual content, scale, and shape of environmental boundaries for two environments have been extensively examined for their impact on the recurrence of spatially ...specific hippocampal firing patterns across environments and across multiple regions of a single environment. Although the shapes of paths taken through an environment are known to impact hippocampal firing patterns within any single region of a single environment, it is not known to what extent path shape and scale can impact firing pattern recurrence across two environments and across multiple regions of a single environment. This question was addressed in the present work where the spatial firing patterns of hippocampal CA1 neurons were examined as rats traversed differently shaped spiral paths centered on the same position within a visually observable curtained enclosure. On such tracks, firing fields for CA1 neurons were found to recur across multiple subregions of a single path and across similarly positioned regions of different paths. Both within and across different spiral tracks, the extent of such pattern recurrence was strongly influenced by similarity in the specific sequences of movement directions and locomotor behaviors engendered by different path shapes. The findings demonstrate that the shapes of paths taken through an environment can robustly and dynamically alter both the scale of spatially specific CA1 firing fields and the extent to which they recur across environments.
Goal-directed behaviors require the consideration and expenditure of physical effort. The anterior cingulate cortex (ACC) appears to play an important role in evaluating effort and reward and in ...organizing goal-directed actions. Despite agreement regarding the involvement of the ACC in these processes, the way in which effort-, reward-, and motor-related information is registered by networks of ACC neurons is poorly understood. To contrast ACC responses to effort, reward, and motor behaviors, we trained rats on a reversal task in which the selected paths on a track determined the level of effort or reward. Effort was presented in the form of an obstacle that was climbed to obtain reward. We used single-unit recordings to identify neural correlates of effort- and reward-guided behaviors. During periods of outcome anticipation, 52% of recorded ACC neurons responded to the specific route taken to the reward while 21% responded prospectively to effort and 12% responded prospectively to reward. In addition, effort- and reward-selective neurons typically responded to the route, suggesting that these cells integrated motor-related activity with expectations of future outcomes. Furthermore, the activity of ACC neurons did not discriminate between choice and forced trials or respond to a more generalized measure of outcome value. Nearly all neural responses to effort and reward occurred after path selection and were restricted to discrete temporal/spatial stages of the task. Together, these findings support a role for the ACC in integrating route-specific actions, effort, and reward in the service of sustaining discrete movements through an effortful series of goal-directed actions.
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