Biology subjects

Buffalo, E. A.

Publications and source records attributed to Buffalo, E. A..

12 recordsLinked to original sources

bioRxiv2026

Physiological landmarks reveal the laminar organization of the primate hippocampus

The laminar anatomy of the hippocampal microcircuit is conserved across mammals, and its physiology has been characterized extensively in rodents, yet how this circuitry is organized physiologically in the primate brain remains poorly understood. Here we used high-density Neuropixels probes to record simultaneously across the subfields of CA1, CA3 and the dentate gyrus in two awake macaques. Sharp-wave ripples and dentate spikes produced current source density signatures that provided physiological landmarks for CA1 and the dentate gyrus, enabling alignment of recordings to hippocampal cytoarchitecture. Theta-band (3-7 Hz) oscillatory activity occurred in discrete bouts whose prevalence peaked in the stratum lacunosum-moleculare. In CA1, gamma-band amplitude was modulated by theta-band phase, with fast and slow gamma preferentially coupled to distinct phases of the theta cycle. Putative principal cells and two interneuron classes differed systematically in firing rate, burstiness, and rhythmic modulation, with principal cells showing theta-rhythmic firing and wide-waveform interneurons showing alpha- and beta-rhythmic firing. Cross-correlogram analyses revealed sparse, distance-dependent functional coupling with a consistent directional hierarchy in which principal cells led interneurons. Together, these results identify the laminar microcircuit organization of the primate hippocampus in vivo and provide a new physiological framework for interpreting primate hippocampal recordings.

neuroscience↗

bioRxiv2026

Neural representations of beliefs in a multi-dimensional inference task

Adaptive behavior requires maintaining and updating probabilistic beliefs about the world, yet how distributed brain circuits implement such computations remains unknown. We recorded from over 1,400 neurons across six brain regions in monkeys performing a multi-dimensional inference task requiring them to infer hidden rules through trial-and-error learning. Behavior was well-described by models based on Bayesian updating of beliefs over rule features. Neural representations of both observable variables (stimuli, rewards) and latent beliefs (rule preferences, confidence) were broadly distributed across hippocampus, amygdala, prefrontal cortex, anterior cingulate, striatum, and inferior temporal cortex. Belief representations were present throughout all task periods but exhibited region- and epoch-specific dynamics. Critically, trial-to-trial changes in population activity reflected Bayesian belief updating: neural responses evolved according to the integration of prior beliefs with new evidence. Additionally, we identified confidence representations that were independent of specific beliefs and showed distinct temporal profiles. These results demonstrate that probabilistic inference emerges from coordinated dynamics across distributed brain systems, with different regions contributing flexibly according to computational demands at different states of learning and decision-making.

neuroscience↗

bioRxiv2025

The Primate Hippocampus Constructs a Temporal Scaffold Anchored to Behavioral Events

The hippocampus has been attributed a range of divergent functions, including roles in memory1,2 and navigation3-5, but how its moment-to-moment neuronal activity supports cognition remains poorly understood. The activity of individual hippocampal neurons is correlated with numerous perceptual features and task variables6-14, raising the question of whether these response properties reflect distinct mechanisms or support a single generalized computation. Here, we show that these diverse response properties reflect a unified organizing principle in which the hippocampus segments experience into discrete events, with population activity transitioning between discrete neural states at behaviorally salient moments. Recording from monkeys performing a virtual spatial alternation task, we found that population activity did not evolve smoothly over time but instead shifted abruptly at each relevant event. These discontinuities segmented activity into distinct ensembles, effectively chunking separate task epochs. Notably, many neuronal responses persisted across visually distinct environments, demonstrating that these dynamics reflect abstract task structure rather than specific sensory features. These results reveal that the hippocampus constructs a temporal scaffold anchored to relevant behavioral events, with each neural state tracking a distinct task phase. This organizational principle may explain the diverse neural correlates observed across studies: rather than individually encoding perceptual or behavioral variables, hippocampal neurons collectively signal the current phase of a behavioral sequence. Our findings suggest that the hippocampus parses experience into meaningful elements and tracks "position" within a learned behavioral structure.

neuroscience↗

bioRxiv2024

Parallel patterns of cognitive aging in marmosets and macaques

As humans age, some experience cognitive impairment while others do not. When impairment does occur, it is not expressed uniformly across cognitive domains and varies in severity across individuals. Translationally relevant model systems are critical for understanding the neurobiological drivers of this variability, which is essential to uncovering the mechanisms underlying the brains susceptibility to the effects of aging. As such, non-human primates are particularly important due to shared behavioral, neuroanatomical, and age-related neuropathological features with humans. For many decades, macaque monkeys have served as the primary non-human primate model for studying the neurobiology of cognitive aging. More recently, the common marmoset has emerged as an advantageous model for this work due to its short lifespan that facilitates longitudinal studies. Despite their growing popularity as a model, whether marmosets exhibit patterns of age-related cognitive impairment comparable to those observed in macaques and humans remains unexplored. To address this major limitation for the development and evaluation of the marmoset as a model of cognitive aging, we directly compared working memory ability as a function of age in macaques and marmosets on the identical working memory task. Our results demonstrate that marmosets and macaques exhibit remarkably similar age-related working memory deficits, highlighting the value of the marmoset as a model for cognitive aging research within the neuroscience community.

animal behavior and cognition↗

bioRxiv2023

Non-Stationary Dynamic Mode Decomposition

Many physical processes display complex high-dimensional time-varying behavior, from global weather patterns to brain activity. An outstanding challenge is to express high dimensional data in terms of a dynamical model that reveals their spatiotemporal structure. Dynamic Mode Decomposition is a means to achieve this goal, allowing the identification of key spatiotemporal modes through the diagonalization of a finite dimensional approximation of the Koopman operator. However, DMD methods apply best to time-translationally invariant or stationary data, while in many typical cases, dynamics vary across time and conditions. To capture this temporal evolution, we developed a method, Non-Stationary Dynamic Mode Decomposition (NS-DMD), that generalizes DMD by fitting global modulations of drifting spatiotemporal modes. This method accurately predicts the temporal evolution of modes in simulations and recovers previously known results from simpler methods. To demonstrate its properties, the method is applied to multi-channel recordings from an awake behaving non-human primate performing a cognitive task.

neuroscience↗

bioRxiv2023

Comparing rapid rule-learning strategies in humans and monkeys

Inter-species comparisons are key to deriving an understanding of the behavioral and neural correlates of human cognition from animal models. We perform a detailed comparison of macaque monkey and human strategies on an analogue of the Wisconsin Card Sort Test, a widely studied and applied multi-attribute measure of cognitive function, wherein performance requires the inference of a changing rule given ambiguous feedback. We found that well-trained monkeys rapidly infer rules but are three times slower than humans. Model fits to their choices revealed hidden states akin to feature-based attention in both species, and decision processes that resembled a Win-stay lose-shift strategy with key differences. Monkeys and humans test multiple rule hypotheses over a series of rule-search trials and perform inference-like computations to exclude candidates. An attention-set based learning stage categorization revealed that perseveration, random exploration and poor sensitivity to negative feedback explain the under-performance in monkeys.

animal behavior and cognition↗

bioRxiv2022

Multiple memory systems for efficient temporal order memory

We report the distinct contribution of multiple memory systems to retrieval of the temporal order of events. The neural dynamics related to retrieval of movie scenes revealed that recalling the temporal order of close events elevates hippocampal theta power, like that observed for recalling close spatial relationships. In contrast, recalling far events elevates beta power in the orbitofrontal cortex, reflecting recall based on the overall movie structure.

neuroscience↗

bioRxiv2022

Improving the efficacy and accessibility of intracranial viral vector delivery in non-human primates

Non-human primates (NHPs) are precious resources for cutting edge neuroscientific research, including large-scale viral vector-based experimentation such as optogenetics. We propose to improve surgical outcomes by enhancing surgical preparation practices of convection-enhanced delivery (CED), which is an efficient viral vector infusion technique for large brains such as NHPs. Here we present both real-time and next-day MRI data of CED in the brains of ten NHPs, and we present a quantitative, inexpensive, and practical bench-side model of the in vivo CED data. Our bench-side model is composed of food coloring infused into a transparent agar phantom, and the spread of infusion is optically monitored over time. Our proposed method approximates CED infusions into the cortex, thalamus, medial temporal lobe and caudate nucleus of NHPs, confirmed by MRI data acquired with either gadolinium-based or manganese-based contrast agents co-infused with optogenetic viral vectors. These methods and data serve to guide researchers and surgical team members in key surgical preparations for intracranial viral delivery using CED in NHPs, and thus improve expression targeting and efficacy and, as a result, reduce surgical risks.

neuroscience↗

bioRxiv2021

Elucidating the neural mechanisms of Learning-to-Learn

Learning-to-learn, a progressive speedup of learning while solving a series of similar problems, represents a core process of knowledge acquisition that draws attention in both neuroscience and artificial intelligence. To investigate its underlying brain mechanism, we trained a recurrent neural network model on arbitrary sensorimotor mappings known to depend on the prefrontal cortex. The network displayed an exponential time course of accelerated learning. The neural substrate of a schema emerges within a low-dimensional subspace of population activity; its reuse in new problems facilitates learning by limiting connection weight changes. Our work highlights the weight-driven modifications of the vector field, which determines the population trajectory of a recurrent network and behavior. Such plasticity is especially important for preserving and reusing the learnt schema in spite of undesirable changes of the vector field due to the transition to learning a new problem; the accumulated changes across problems account for the learning-to-learn dynamics.

neuroscience↗

bioRxiv2019

A temporal record of the past with a spectrum of time constants in the monkey entorhinal cortex

Episodic memory is believed to be intimately related to our experience of the passage of time. Indeed, neurons in the hippocampus and other brain regions critical to episodic memory code for the passage of time at a range of time scales. The origin of this temporal signal, however, remains unclear. Here, we examined temporal responses in the entorhinal cortex of macaque monkeys as they viewed complex images. Many neurons in the entorhinal cortex were responsive to image onset, showing large deviations from baseline firing shortly after image onset but relaxing back to baseline at different rates. This range of relaxation rates allowed for the time since image onset to be decoded on the scale of seconds. Further, these neurons carried information about image content, suggesting that neurons in the entorhinal cortex carry information not only about when an event took place but also the identity of that event. Taken together, these findings suggest that the primate entorhinal cortex uses a spectrum of time constants to construct a temporal record of the past in support of episodic memory.

neuroscience↗

bioRxiv2017

Entorhinal cortex receptive fields are modulated by spatial attention, even without movement.

Grid cells have been identified in the entorhinal cortex in a variety of species and allow for the precise decoding of position in space (1-7). Along with potentially playing an important role in navigation, grid cells have recently been hypothesized to make a general contribution to mental operations, including remembering the past and thinking about the future (8,9). A prerequisite for this hypothesis is that grid cell activity does not critically depend on physical movement. Directed attention, which contributes to virtually all mental operations and can be separated from physical movement provides a good test case to investigate this hypothesis. Overt attention in the form of fixational eye movements leads to grid-like firing fields in the monkey entorhinal cortex (3). Here we show that movement of covert attention, without any physical movement, also elicits spatial receptive fields with a triangular tiling of the space. In monkeys trained to maintain central fixation while covertly attending to a stimulus moving in the periphery we identified a significant population (20/141, 14% neurons at a FDR<5%) of entorhinal cells with spatially structured receptive fields. Further, we were able to identify a population of neurons that were labeled as grid cells on an individual basis. This contrast with our recordings obtained in the hippocampus, where grid-like representations were not observed. Our results provide compelling evidence that neurons in macaque entorhinal cortex do not rely on physical movement. Notably, these results support the notion that grid cells may be capable of serving a variety of different cognitive functions and suggest that grid cells are a versatile component of many neural algorithms.

neuroscience↗

bioRxiv2017

Neurons in primate entorhinal cortex represent gaze position in multiple spatial reference frames

Primates predominantly rely on vision to gather information from the environment, and neurons representing visual space and gaze position are found in many brain areas. Within the medial temporal lobe, a brain region critical for memory, neurons in the entorhinal cortex of macaque monkeys exhibit spatial selectivity for gaze position. Specifically, the firing rate of single neurons reflects fixation location within a visual image (Killian et al., 2012). In the rodents, entorhinal cells such as grid cells, border cells, and head direction cells show spatial representations aligned to visual environmental features instead of the body (Hafting et al., 2005, Solstad et al. 2008, Sargolini et al., 2006, Diehl et al., 2017). However, it is not known whether similar allocentric representations exist in primate entorhinal cortex. Here, we recorded neural activity in the entorhinal cortex in two male rhesus monkeys during a naturalistic, free-viewing task. Our data reveal that a majority of entorhinal neurons represent gaze position, and that simultaneously recorded neurons exhibit distinct spatial reference frames, with some neurons aligning to the visual image and others aligning to the monkeys head position. Our results also show that entorhinal neural activity can be used to predict gaze position with a high degree of accuracy. These findings demonstrate that visuospatial representation is a fundamental property of entorhinal neurons in primates, and suggest that entorhinal cortex may support relational memory and motor planning by coding attentional locus in distinct, behaviorally relevant frames of reference.\n\nSignificance StatementThe entorhinal cortex, a brain area important for memory, shows striking spatial activity in rodents through grid cells, border cells, head direction cells, and nongrid spatial cells. The majority of entorhinal neurons signal the location of a rodent relative to visual environmental cues, representing the location of the animal relative to space in the world instead of the body. Recently, our laboratory found that entorhinal neurons can signal location of gaze while a monkey visually explores images. Here, we report that spatial entorhinal neurons are widespread in the monkey, and these neurons are capable of showing a world-based spatial reference frame locked to the bounds of explored images. These results help connect the extensive findings in rodents to the primate.

neuroscience↗