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Animals in the natural world constantly encounter geometrically complex landscapes. Successful navigation requires that they understand geometric features of these landscapes, including boundaries, landmarks, corners and curved areas, all of which collectively define the geometry of the environment1-12. Crucial to the reconstruction of the geometric layout of natural environments are concave and convex features, such as corners and protrusions. However, the neural substrates that could underlie the perception of concavity and convexity in the environment remain elusive. Here we show that the dorsal subiculum contains neurons that encode corners across environmental geometries in an allocentric reference frame. Using longitudinal calcium imaging in freely behaving mice, we find that corner cells tune their activity to reflect the geometric properties of corners, including corner angles, wall height and the degree of wall intersection. A separate population of subicular neurons encode convex corners of both larger environments and discrete objects. Both corner cells are non-overlapping with the population of subicular neurons that encode environmental boundaries. Furthermore, corner cells that encode concave or convex corners generalize their activity such that they respond, respectively, to concave or convex curvatures within an environment. Together, our findings suggest that the subiculum contains the geometric information needed to reconstruct the shape and layout of naturalistic spatial environments.

Hippocampal CA1 neuronal ensembles generate sequential patterns of firing activity that contribute to episodic memory formation and spatial cognition. Here we used in vivo calcium imaging to record neural ensemble activities in mouse hippocampal CA1 and identified CA1 excitatory neuron sub-populations whose members are active across the same second-long period of time. We identified groups of hippocampal neurons sharing temporally correlated neural calcium activity during behavioral exploration and found that they also organized as clusters in anatomical space. Such clusters vary in membership and activity dynamics with respect to movement in different environments, but also appear during immobility in the dark suggesting an internal dynamic. The strong covariance between dynamics and anatomical location within the CA1 sub-region reveals a previously unrecognized form of topographic representation in hippocampus that may guide generation of hippocampal sequences across time and therefore organize the content of episodic memory.

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.

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

The study behavioral phenomena and the brain states which accompany these behaviors has a long history. The fields of neuroscience and behavioral psychology have, for over 100 years, utilized structured mazes in their work in order to probe how animals choose to navigate them, and how neuron activity reflects navigational features of the environment. This dissertation proposes that appreciating similar places within an environment requires a structurally complex environment to appreciate. Evidence that structural complexity ought to elicit novel neural and behavioral phenomena is substantial. There is evidence that subiculum (SUB) neurons respond in a spatial manner similarly across different environments that share general structural complexity, and present unique directional tuning only on structured mazes. There is also evidence that less explicit structure in an open environment can drastically modulate activity in posterior parietal cortex (PPC) neurons. Both of these brain regions lay along an anatomical circuit connecting the hippocampal formation (HPC) to motor-output regions of the brain. Furthermore it is known that alternation behavior (AB), while reliable, is readily modulated by environmental factors in simple structures. To address deficiencies in investigating these systems this dissertation employs both a structured maze, the triple-T, alongside a working memory task which allows for the animal to self-organize a strategy; thus providing structure in two forms, one explicit with the maze, and one implicit with the reward contingencies. Unique representations of place-analogies, and structural route-similarity are reported from SUB and PPC respectively. These reports alongside a report of AB being organized by spatial location provide a functional framework for the utility of appreciating similar places in complex spaces. This dissertation describes the neural correlates of brain regions anatomically crucial to a space-to-action circuit while animals

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.

The study behavioral phenomena and the brain states which accompany these behaviors has a long history. The fields of neuroscience and behavioral psychology have, for over 100 years, utilized structured mazes in their work in order to probe how animals choose to navigate them, and how neuron activity reflects navigational features of the environment. This dissertation proposes that appreciating similar places within an environment requires a structurally complex environment to appreciate. Evidence that structural complexity ought to elicit novel neural and behavioral phenomena is substantial. There is evidence that subiculum (SUB) neurons respond in a spatial manner similarly across different environments that share general structural complexity, and present unique directional tuning only on structured mazes. There is also evidence that less explicit structure in an open environment can drastically modulate activity in posterior parietal cortex (PPC) neurons. Both of these brain regions lay along an anatomical circuit connecting the hippocampal formation (HPC) to motor-output regions of the brain. Furthermore it is known that alternation behavior (AB), while reliable, is readily modulated by environmental factors in simple structures. To address deficiencies in investigating these systems this dissertation employs both a structured maze, the triple-T, alongside a working memory task which allows for the animal to self-organize a strategy; thus providing structure in two forms, one explicit with the maze, and one implicit with the reward contingencies. Unique representations of place-analogies, and structural route-similarity are reported from SUB and PPC respectively. These reports alongside a report of AB being organized by spatial location provide a functional framework for the utility of appreciating similar places in complex spaces. This dissertation describes the neural correlates of brain regions anatomically crucial to a space-to-action circuit while animals

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.

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

The hippocampal formation (HF) is well documented as having a feedforward, unidirectional circuit organization termed the trisynaptic pathway. This circuit organization exists along the septotemporal axis of the HF, but the circuit connectivity across septal to temporal regions is less well described. The emergence of viral genetic mapping techniques enhances our ability to determine the detailed complexity of HF circuitry. In earlier work, we mapped a subiculum (SUB) back projection to CA1 prompted by the discovery of theta wave back propagation from the SUB to CA1 and CA3. We reason that this circuitry may represent multiple extended noncanonical pathways involving the subicular complex and hippocampal subregions CA1 and CA3. In the present study, multiple retrograde viral tracing approaches produced robust mapping results, which supports this prediction. We find significant noncanonical synaptic inputs to dorsal hippocampal CA3 from ventral CA1 (vCA1), perirhinal cortex (Prh), and the subicular complex. Thus, CA1 inputs to CA3 run opposite the trisynaptic pathway and in a temporal to septal direction. Our retrograde viral tracing results are confirmed by anterograde-directed viral mapping of projections from input mapped regions to hippocampal dorsal CA3 (dCA3). We find that genetic inactivation of the projection of vCA1 to dCA3 impairs object-related spatial learning and memory but does not modulate anxiety-related behaviors. Our data provide a circuit foundation to explore novel functional roles contributed by these noncanonical hippocampal circuit connections to hippocampal circuit dynamics and learning and memory behaviors.

The hippocampal formation (HF) is well documented as having a feedforward, unidirectional circuit organization termed the trisynaptic pathway. This circuit organization exists along the septotemporal axis of the HF, but the circuit connectivity across septal to temporal regions is less well described. The emergence of viral genetic mapping techniques enhances our ability to determine the detailed complexity of HF circuitry. In earlier work, we mapped a subiculum (SUB) back projection to CA1 prompted by the discovery of theta wave back propagation from the SUB to CA1 and CA3. We reason that this circuitry may represent multiple extended noncanonical pathways involving the subicular complex and hippocampal subregions CA1 and CA3. In the present study, multiple retrograde viral tracing approaches produced robust mapping results, which supports this prediction. We find significant noncanonical synaptic inputs to dorsal hippocampal CA3 from ventral CA1 (vCA1), perirhinal cortex (Prh), and the subicular complex. Thus, CA1 inputs to CA3 run opposite the trisynaptic pathway and in a temporal to septal direction. Our retrograde viral tracing results are confirmed by anterograde-directed viral mapping of projections from input mapped regions to hippocampal dorsal CA3 (dCA3). We find that genetic inactivation of the projection of vCA1 to dCA3 impairs object-related spatial learning and memory but does not modulate anxiety-related behaviors. Our data provide a circuit foundation to explore novel functional roles contributed by these noncanonical hippocampal circuit connections to hippocampal circuit dynamics and learning and memory behaviors.

Animals ranging from rats to humans can demonstrate cognitive map capabilities. We evolved weights in a biologically plausible recurrent neural network (RNN) using an evolutionary algorithm to replicate the behavior and neural activity observed in rats during a spatial and working memory task in a triple T-maze. The rat was simulated in the Webots robot simulator and used vision, distance and accelerometer sensors to navigate a virtual maze. After evolving weights from sensory inputs to the RNN, within the RNN, and from the RNN to the robot's motors, the Webots agent successfully navigated the space to reach all four reward arms with minimal repeats before time-out. Our current findings suggest that it is the RNN dynamics that are key to performance, and that performance is not dependent on any one sensory type, which suggests that neurons in the RNN are performing mixed selectivity and conjunctive coding. Moreover, the RNN activity resembles spatial information and trajectory-dependent coding observed in the hippocampus. Collectively, the evolved RNN exhibits navigation skills, spatial memory, and working memory. Our method demonstrates how the dynamic activity in evolved RNNs can capture interesting and complex cognitive behavior and may be used to create RNN controllers for robotic applications.

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.

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.

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.

Physiological studies suggest spatial representation gradients along the CA1 proximodistal axis. To determine the underlying anatomical basis, we quantitatively mapped canonical and noncanonical inputs to excitatory neurons in dorsal hippocampal CA1 along the proximal-distal axis in mice of both sexes using monosynaptic rabies tracing. Our quantitative analyses show comparable strength of subiculum complex and entorhinal cortex (EC) inputs to CA1, significant inputs from presubiculum and parasubiculum to CA1, and a threefold stronger input to proximal versus distal CA1 from CA3. Noncanonical subicular complex inputs exhibit opposing topographic connectivity gradients whereby the subiculum-CA1 input strength systematically increases but the presubiculum-CA1 input strength decreases along the proximal-distal axis. The subiculum input strength cotracks that of the lateral EC, known to be less spatially selective than the medial EC. The functional significance of this organization is verified physiologically for subiculum-to-CA1 inputs. These results reveal a novel anatomical framework by which to determine the circuit bases for CA1 representations.

Physiological studies suggest spatial representation gradients along the CA1 proximodistal axis. To determine the underlying anatomical basis, we quantitatively mapped canonical and noncanonical inputs to excitatory neurons in dorsal hippocampal CA1 along the proximal-distal axis in mice of both sexes using monosynaptic rabies tracing. Our quantitative analyses show comparable strength of subiculum complex and entorhinal cortex (EC) inputs to CA1, significant inputs from presubiculum and parasubiculum to CA1, and a threefold stronger input to proximal versus distal CA1 from CA3. Noncanonical subicular complex inputs exhibit opposing topographic connectivity gradients whereby the subiculum-CA1 input strength systematically increases but the presubiculum-CA1 input strength decreases along the proximal-distal axis. The subiculum input strength cotracks that of the lateral EC, known to be less spatially selective than the medial EC. The functional significance of this organization is verified physiologically for subiculum-to-CA1 inputs. These results reveal a novel anatomical framework by which to determine the circuit bases for CA1 representations.

Episodic memories are inherently spatial experiences. This is reflected in the neural implementation of space and memory in mammals, where the hippocampus is a cortical structure necessary for successful spatial navigation and encoding of episodic memories. While the spatial encoding properties in this region are well studied in rodents, the neural pathway that allows these representations to utilize this information and shape navigation behavior is not well understood. This dissertation proposes a dorsal navigation circuit from subregion CA1 of the hippocampus through to primary motor cortex. This cortical circuit passes through subiculum (SUB) and entorhinal cortex (EC), the two main output structures of hippocampus, before proceeding through retrosplenial (RSP) and posterior parietal (PPC) cortices. Both of these regions reciprocally connect to the premotor medial precentral cortex (MPC), a premotor cortex of the rat that projects directly to primary motor cortex. Evidence of the navigational utility of these regions is substantial. Lesion studies show that RSP, SUB, and EC are all necessary for full performance of hippocampus-dependent spatial navigation. PPC shows deficits more consistent with spatially driven action planning, while MPC lesions cause laterality bias in choices. Neural representations support the proposed circuit with unique spatial representations in EC, RSP, and PPC. Spatial representations in SUB and MPC, however, are not well studied in during navigation. To address the knowledge deficiencies in the proposed circuit, this dissertation contains electrophysiology studies of SUB and MPC during a complex navigation task. In SUB, a novel form of spatial encoding encoded the axis of travel. This neural population shows temporal firing properties consistent with an integrated role with hippocampus. In MPC, action encoding dominated neural representations across spatial and choice contexts. A widespread spatial signal was also present in the region.

The Social Intelligence Hypothesis proposes that the kind of complex cognition observed in humans and other species co-evolved with complex societies. Research focusing on this topic has been conducted mostly on primates, with a significant body of work conducted under the ‘Machiavellian Intelligence’ program. To further understand this relationship, there may be utility in looking beyond non-human primates to a species whose social complexity may be more similar to our own than any extant primate, with an updated methodological approach. Male bottlenose dolphins in Shark Bay, Western Australia, participate in up to three levels of alliance formation within a large society of resident dolphins. This nested structure of alliances may be the most complex outside of humans, but to date little is known about third-order alliances, or how alliance relationships may be mediated through social interaction. This study focused on the relationships among 24 male allies within this system over a six-year period of time to address two principal questions: (1) how are third-order alliances structured, what are their dynamics, and how do they respond to change? (2) how do the particular kinds of behavioral interactions that allies engage in relate to the observed structure and dynamics of the alliance network? I found that the alliance network demonstrated features of complex systems including local segregation and global integration, dynamic (non-linear) change, and the presence of social roles. The relationship between social complexity and social cognition was indicated by the range of interactions observed, as well as variability in when and with whom these interactions occurred. For example, second-order allies who frequently associated together engaged in higher rates of synchrony and affiliative contact. At a context hypothesized to have higher uncertainty (group joining events, or fusions), I found higher rates of social vocalizations, and higher rates affiliative interac

Episodic memories are inherently spatial experiences. This is reflected in the neural implementation of space and memory in mammals, where the hippocampus is a cortical structure necessary for successful spatial navigation and encoding of episodic memories. While the spatial encoding properties in this region are well studied in rodents, the neural pathway that allows these representations to utilize this information and shape navigation behavior is not well understood. This dissertation proposes a dorsal navigation circuit from subregion CA1 of the hippocampus through to primary motor cortex. This cortical circuit passes through subiculum (SUB) and entorhinal cortex (EC), the two main output structures of hippocampus, before proceeding through retrosplenial (RSP) and posterior parietal (PPC) cortices. Both of these regions reciprocally connect to the premotor medial precentral cortex (MPC), a premotor cortex of the rat that projects directly to primary motor cortex. Evidence of the navigational utility of these regions is substantial. Lesion studies show that RSP, SUB, and EC are all necessary for full performance of hippocampus-dependent spatial navigation. PPC shows deficits more consistent with spatially driven action planning, while MPC lesions cause laterality bias in choices. Neural representations support the proposed circuit with unique spatial representations in EC, RSP, and PPC. Spatial representations in SUB and MPC, however, are not well studied in during navigation. To address the knowledge deficiencies in the proposed circuit, this dissertation contains electrophysiology studies of SUB and MPC during a complex navigation task. In SUB, a novel form of spatial encoding encoded the axis of travel. This neural population shows temporal firing properties consistent with an integrated role with hippocampus. In MPC, action encoding dominated neural representations across spatial and choice contexts. A widespread spatial signal was also present in the region.

The Social Intelligence Hypothesis proposes that the kind of complex cognition observed in humans and other species co-evolved with complex societies. Research focusing on this topic has been conducted mostly on primates, with a significant body of work conducted under the ‘Machiavellian Intelligence’ program. To further understand this relationship, there may be utility in looking beyond non-human primates to a species whose social complexity may be more similar to our own than any extant primate, with an updated methodological approach. Male bottlenose dolphins in Shark Bay, Western Australia, participate in up to three levels of alliance formation within a large society of resident dolphins. This nested structure of alliances may be the most complex outside of humans, but to date little is known about third-order alliances, or how alliance relationships may be mediated through social interaction. This study focused on the relationships among 24 male allies within this system over a six-year period of time to address two principal questions: (1) how are third-order alliances structured, what are their dynamics, and how do they respond to change? (2) how do the particular kinds of behavioral interactions that allies engage in relate to the observed structure and dynamics of the alliance network? I found that the alliance network demonstrated features of complex systems including local segregation and global integration, dynamic (non-linear) change, and the presence of social roles. The relationship between social complexity and social cognition was indicated by the range of interactions observed, as well as variability in when and with whom these interactions occurred. For example, second-order allies who frequently associated together engaged in higher rates of synchrony and affiliative contact. At a context hypothesized to have higher uncertainty (group joining events, or fusions), I found higher rates of social vocalizations, and higher rates affiliative interac

Cortically projecting basal forebrain neurons play a critical role in learning and attention, and their degeneration accompanies age-related impairments in cognition. Despite the impressive anatomical and cell-type complexity of this system, currently available data suggest that basal forebrain neurons lack complexity in their response fields, with activity primarily reflecting only macro-level brain states such as sleep and wake, onset of relevant stimuli and/or reward obtainment. The current study examined the spiking activity of basal forebrain neuron populations across multiple phases of a selective attention task, addressing, in particular, the issue of complexity in ensemble firing patterns across time. Clustering techniques applied to the full population revealed a large number of distinct categories of task-phase-specific activity patterns. Unique population firing-rate vectors defined each task phase and most categories of task-phase-specific firing had counterparts with opposing firing patterns. An analogous set of task-phase-specific firing patterns was also observed in a population of posterior parietal cortex neurons. Thus, consistent with the known anatomical complexity, basal forebrain population dynamics are capable of differentially modulating their cortical targets according to the unique sets of environmental stimuli, motor requirements, and cognitive processes associated with different task phases.

Cortically projecting basal forebrain neurons play a critical role in learning and attention, and their degeneration accompanies age-related impairments in cognition. Despite the impressive anatomical and cell-type complexity of this system, currently available data suggest that basal forebrain neurons lack complexity in their response fields, with activity primarily reflecting only macro-level brain states such as sleep and wake, onset of relevant stimuli and/or reward obtainment. The current study examined the spiking activity of basal forebrain neuron populations across multiple phases of a selective attention task, addressing, in particular, the issue of complexity in ensemble firing patterns across time. Clustering techniques applied to the full population revealed a large number of distinct categories of task-phase-specific activity patterns. Unique population firing-rate vectors defined each task phase and most categories of task-phase-specific firing had counterparts with opposing firing patterns. An analogous set of task-phase-specific firing patterns was also observed in a population of posterior parietal cortex neurons. Thus, consistent with the known anatomical complexity, basal forebrain population dynamics are capable of differentially modulating their cortical targets according to the unique sets of environmental stimuli, motor requirements, and cognitive processes associated with different task phases.

Learning to ignore irrelevant stimuli is essential to achieving efficient and fluid attention, and serves as the complement to increasing attention to relevant stimuli. The different cholinergic (ACh) subsystems within the basal forebrain regulate attention in distinct but complementary ways. ACh projections from the substantia innominata/nucleus basalis region (SI/nBM) to the neocortex are necessary to increase attention to relevant stimuli and have been well studied. Lesser known are ACh projections from the medial septum/vertical limb of the diagonal band (MS/VDB) to the hippocampus and the cingulate that are necessary to reduce attention to irrelevant stimuli. We developed a neural simulation to provide insight into how ACh can decrement attention using this distinct pathway from the MS/VDB. We tested the model in behavioral paradigms that require decremental attention. The model exhibits behavioral effects such as associative learning, latent inhibition, and persisting behavior. Lesioning the MS/VDB disrupts latent inhibition, and drastically increases perseverative behavior. Taken together, the model demonstrates that the ACh decremental pathway is necessary for appropriate learning and attention under dynamic circumstances and suggests a canonical neural architecture for decrementing attention.