Biology subjects

Kramer, L. E.

Publications and source records attributed to Kramer, L. E..

6 recordsLinked to original sources

bioRxiv2026

Sequential experience reshapes population representations in visual cortex

Visual experience is organized in time. When riding the same bus route each day, the visual scene unfolds in a predictable order without requiring active choice. During goal-directed behavior, individuals organize actions into routines, such as repeatedly walking the same route to work even when alternatives are equally efficient. Because experience unfolds across sequences of events, identifying how it reshapes population activity requires examining representations over time. Many studies have shown that repeated experience reduces mean firing rates in visual cortex1-14. While firing rates effectively signal novelty or repetition, they are not well positioned to describe how populations of neurons represent temporal relationships. A growing body of work suggests that the geometry of population activity provides additional insight into how visual information is structured and read out15-26. We examined how experience with temporal structure reshapes the geometry of population activity in visual area V4. We recorded neuronal populations across three contexts that varied in temporal structure and behavioral relevance: repeated presentation of individual images, passive exposure to structured image sequences, and repeated execution of self-chosen visually guided action sequences for reward. Across contexts, experience constrained population responses toward a typical activity pattern. In sequence contexts, experience made temporal position more linearly accessible and, during active practice, increased the separability of task-relevant variables. These findings show that experience reorganizes the geometry of visual population activity to reflect temporal structure, constraining responses and altering how sequence-related information is represented.

neuroscience↗

bioRxiv2024

Task interference as a neuronal basis for the cost of cognitive flexibility

Humans and animals have an impressive ability to juggle multiple tasks in a constantly changing environment. This flexibility, however, worsens performance under uncertain task conditions. Here, we combined monkey electrophysiology, human psychophysics, and artificial neural network modeling to investigate the neuronal mechanisms underlying this performance cost. We developed a behavioural paradigm to measure and influence participants decision-making and perception in two distinct perceptual tasks. Our data reveal that both humans and monkeys, unlike an artificial neural network trained for the same tasks, make less accurate perceptual decisions when the task is uncertain. We generated a mechanistic hypothesis by comparing this neural network trained to produce correct choices with another network trained to replicate the participants choices. We hypothesized, and confirmed with further behavioural, physiological, and causal experiments, that the cost of task uncertainty and flexibility comes from what we term feature interference. Under uncertain conditions, interference between different tasks causes errors because it results in stronger representations of irrelevant features and entangled neuronal representations of different features. Our results suggest a tantalizing, general hypothesis: that cognitive capacity limitations, both in health and disease, stem from interference between neural representations of different stimuli, tasks, or memories.

neuroscience↗

bioRxiv2023

Contributions of early and mid-level visual cortex to high-level object categorization

The complexity of visual features for which neurons are tuned increases from early to late stages of the ventral visual stream. Thus, the standard hypothesis is that high-level functions like object categorization are primarily mediated by higher visual areas because they require more complex image formats that are not evident in early visual processing stages. However, human observers can categorize images as objects or animals or as big or small even when the images preserve only some low- and mid-level features but are rendered unidentifiable ( texforms, Long et al., 2018). This observation suggests that even the early visual cortex, in which neurons respond to simple stimulus features, may already encode signals about these more abstract high-level categorical distinctions. We tested this hypothesis by recording from populations of neurons in early and mid-level visual cortical areas while rhesus monkeys viewed texforms and their unaltered source stimuli (simultaneous recordings from areas V1 and V4 in one animal and separate recordings from V1 and V4 in two others). Using recordings from a few dozen neurons, we could decode the real-world size and animacy of both unaltered images and texforms. Furthermore, this neural decoding accuracy across stimuli was related to the ability of human observers to categorize texforms by real-world size and animacy. Our results demonstrate that neuronal populations early in the visual hierarchy contain signals useful for higher-level object perception and suggest that the responses of early visual areas to simple stimulus features display preliminary untangling of higher-level distinctions.

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bioRxiv2021

Dynamic task-belief is an integral part of decision-making

Natural decisions involve two seemingly separable processes: inferring the relevant task (task-belief) and performing the believed-relevant task. The assumed separability has led to the traditional practice of studying task-switching and perceptual decision-making individually. Here, we used a novel paradigm to manipulate and measure macaque monkeys task-belief, and demonstrated inextricable neuronal links between flexible task-belief and perceptual decision-making. We showed that in animals, but not artificial networks that performed as well or better than the animals, stronger task-belief is associated with better perception. Correspondingly, recordings from neuronal populations in cortical areas 7a and V1 revealed that stronger task-belief is associated with better discriminability of the believed-relevant but not the believed-irrelevant feature. Perception also impacts belief updating: noise fluctuations in V1 help explain how task-belief is updated. Our results demonstrate that complex tasks and multi-area recordings can reveal fundamentally new principles of how biology affects behavior in health and disease.

neuroscience↗

bioRxiv2020

Cocaine triggers glial-mediated synaptogenesis

Synaptogenesis is essential in forming new neurocircuits during development, and this is mediated in part by astrocyte-released thrombospondins (TSPs) and activation of their neuronal receptor, 2{delta}-1. Here, we show that this developmental synaptogenic mechanism is utilized during cocaine experience to induce spinogenesis and the generation of AMPA receptor-silent glutamatergic synapses in the adult nucleus accumbens (NAc). Specifically, cocaine administration activates NAc astrocytes, and preventing this activation blocks cocaine-induced generation of silent synapses. Furthermore, knockout of TSP2, or pharmacological inhibition or viral-mediated knockdown of 2{delta}-1, prevents cocaine-induced generation of silent synapses. Moreover, disrupting TSP2-2{delta}-1-mediated spinogenesis and silent synapse generation in the NAc occludes cue-induced cocaine seeking after withdrawal from cocaine self-administration and cue-induced reinstatement of cocaine seeking after drug extinction. These results establish that silent synapses are generated by an astrocyte-mediated synaptogenic mechanism in response to cocaine experience and embed critical cue-associated memory traces that promote cocaine relapse.

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bioRxiv2019

Low rank mechanisms underlying flexible visual representations

Neuronal population responses to sensory stimuli are remarkably flexible. The responses of neurons in visual cortex depend on stimulus properties (e.g. contrast), processes that affect all stages of visual processing (e.g. adaptation), and cognitive processes (e.g attention or task switching). The effects of all of these processes on trial-averaged responses of individual neurons are well-described by divisive normalization, in which responses are scaled by the total stimulus drive. Normalization describes how a staggering variety of sensory, cognitive, and motor processes affect individual neurons (1), but whether different normalization processes could be mediated by the same mechanism remains poorly understood. We and others recently showed that attention has low rank effects on the covariability of populations of neurons in visual area V4 (2-4), which strongly constrains mechanistic models mechanism (2). We hypothesized that measuring changes in population covariability associated with other normalization processes could clarify whether they might share a mechanism. Our experimental design included measurements in multiple visual areas using four normalization processes. We found that contrast, adaptation, attention, and task switching affect the responses of populations of neurons in primate visual cortex in a similarly low rank way. These results suggest that a given circuit uses a common mechanism to perform many forms of normalization and likely reflect a general principle that applies to a wide range of brain areas and sensory, cognitive, or motor processes.

neuroscience↗