bioRxiv Science⌕ Search

Biology subjects

Mehta, M. R.

Publications and source records attributed to Mehta, M. R..

7 recordsLinked to original sources

Moving object generates topographic responses in the majority of entorhinal neurons

Vision is crucial in generating a complex array of responses in rodents during spatial exploration and in humans during memory tasks. These tasks involve other variables too, e.g. multisensory cues in rodents and complex memories in humans. Further, there are major differences between the medial and lateral entorhinal cortical (MEC and LEC) functional cell types. To understand the contribution of purely visual information to entorhinal responses, we presented a simple, moving vertical bar of light to head-fixed mice, without any task or reward. Surprisingly, 66% (2391/3601) of the MEC broad spiking neurons were significantly modulated by the bar position on the screen. Visual tuning in MEC had a pronounced dorsoventral topography --the tuning strength dropped from 79% in the dorsal most quartile to 40% in the ventral most quartile. Unlike major differences in spatial and other codes between MEC and LEC during free foraging experiments, LEC cells showed very similar visual tuning (392/606, 65%), including the dorso-ventral gradient in LEC5. Additionally, the majority of putative interneurons, from MEC as well as LEC, showed similar, widespread visual tuning, unlike spatial tasks. Neurons also encoded the object motion direction (naso-temporal vs. temporo-nasal visual motion) with changes in mean rate, tuning strength and/or tuning location. Such directional nature of visual tuning indicates significant history-dependence or sequence encoding. Consistently, replacing the continuous motion by randomly flashing bar of light abolished bar-tuning in two-thirds of continuous bar-tuned cells and substantially altered tuning in the rest. These results reveal the contribution of purely visual inputs in generating anatomically organized responses in the majority of entorhinal neurons. The prevalence and similarity of visual tuning across all layers of MEC as well as LEC exceeds that of other known functional cell types (like grid cells in MEC or egocentric object tuning/time-cells in LEC) during spatial navigation tasks and could be foundational in understanding entorhinal complexity.

neuroscience↗

Hippocampal trace coding dominates and disrupts place coding

The hippocampus is widely viewed as a spatial map because many CA1 neurons exhibit spatially selective activity during exploration. However, the hippocampus is also involved in nonspatial learning, including conditioning tasks. Most prior reports of nonspatial hippocampal activity were obtained in immobile animals, leading to the proposal that the hippocampus encodes spatial variables during locomotion and nonspatial variables during immobility. The question of how the hippocampus encodes both spatial and nonspatial variables during locomotion and spatial exploration has remained unanswered. To address this issue directly, we used calcium imaging to record the activity of thousands of CA1 neurons from rats tested on a conditioning task while freely exploring an open field. Across more than 6,000 neurons from five rats, the rate of calcium events increased during conditioning task periods relative to non-task periods, an effect that persisted after controlling for locomotor speed. At the single cell level, conditioning task modulation was widespread and strongly biased toward increased activity; neurons whose activity was enhanced during the conditioning task outnumbered spatially selective neurons by more than threefold. In addition, many neurons showed significantly increased activity during specific segments of the conditioning task. At the population level, conditioning coding remained invariant to changing spatial location; in contrast, spatial coding was reduced during task periods. These findings show that during active behavior, engagement in the conditioning task reorganizes hippocampal activity into a temporally structured pattern of population activity that can dominate and disrupt place coding. Together, these results challenge the view that the hippocampus functions primarily as a stable spatial map.

neuroscience↗

Theory of spontaneous persistent activity and inactivity in vivo reveals differential cortico-entorhinal functional connectivity

Persistent activity is thought to mediate working memory. While such stimulus evoked persistence is well studied, mechanisms of internally generated or spontaneous persistence in vivo are unknown. Further, current theories based on attractor dynamics focus on elevated activity as a memory substrate, while little attention has focused on the role of inactivity attractors. Here, we present a mean field model of functional interaction between large cortical networks that predicts both spontaneous persistent activity (SPA) and inactivity (SPI); the latter has never been seen before in experiments or models. We confirm these predictions using simultaneously recorded neocortical local field potential (LFP) and the membrane potential (Vm) of identified excitatory neurons from several brain areas in vivo during slow oscillations, especially from layer 3 of the medial (MECIII) and lateral entorhinal cortex (LECIII), which show SPA and SPI. By matching model and experimental statistics, we predict the relative strength of internal and external excitation in the LECIII and MECIII networks. Our predictions match anatomical data. Further, the model predicts, and the experiments confirm, that SPA and SPI are quantized by cortical UDS and follow the statistics of a history dependent Bernoulli process. These convergent, theory-experiment results thus reveal the differential nature of cortico-entorhinal functional connectivity, resulting in a unique pattern of persistent activity and persistent inactivity, a novel and energetically efficient memory substrate.

neuroscience↗

Moving bar of light evokes vectorial spatial selectivity in the immobile rat hippocampus

Visual cortical neurons encode the position and motion direction of specific stimuli retrospectively, without any locomotion or task demand1. Hippocampus, a part of visual system, is hypothesized to require self-motion or cognitive task to generate allocentric spatial selectivity that is scalar, abstract2,3, and prospective4-7. To bridge these seeming disparities, we measured rodent hippocampal selectivity to a moving bar of light in a body-fixed rat. About 70% of dorsal CA1 neurons showed stable activity modulation as a function of the bars angular position, independent of behavior and rewards. A third of tuned cells also encoded the direction of revolution. In other experiments, neurons encoded the distance of bar, with preference for approaching motion. Collectively, these demonstrate visually evoked vectorial selectivity (VEVS). Unlike place cells, VEVS was retrospective. Changes in the visual stimulus or its trajectory did not cause remapping but only caused gradual changes. Most VEVS tuned neurons behaved like place cells during spatial exploration and the two selectivity were correlated. Thus, VEVS could form the basic building block of hippocampal activity. When combined with self-motion, reward, or multisensory stimuli8, it can generate the complexity of prospective representations including allocentric space9, time10,11, and episodes12.

neuroscience↗

Hippocampal representations of distance, space, and direction and their plasticity predict navigational performance

The hippocampus is implicated in episodic memory and allocentric spatial navigation. However, spatial selectivity is insufficient to navigate; one needs information about the distance and direction to the reward on a specific journey. The nature of these representations, whether they are expressed in an episodic-like sequence, and their relationship with navigational performance are unknown. We recorded single units from dorsal CA1 of the hippocampus while rats navigated to an unmarked reward zone defined solely by distal visual cues, similar to the classic water maze. The allocentric spatial selectivity was substantially weaker than in typical real world tasks, despite excellent navigational performance. Instead, the majority of cells encoded path distance from the start of trials. Cells also encoded the rats allocentric position and head angle. Often the same cells multiplexed and encoded path distance, head direction and allocentric position in a sequence, thus encoding a journey-specific episode. The strength of neural activity and tuning strongly correlated with performance, with a temporal relationship indicating neural responses influencing behavior and vice versa. Consistent with computational models of associative Hebbian learning, neural responses showed increasing clustering and became better predictors of behaviorally relevant variables, with neurometric curves exceeding and converging to psychometric curves. These findings demonstrate that hippocampal neurons multiplex and exhibit highly plastic, task- and experience-dependent tuning to path-centric and allocentric variables to form an episode, which could mediate navigation.

neuroscience↗

Enhanced hippocampal theta rhythmicity and emergence of eta oscillation in virtual reality

Hippocampal theta oscillations in rodents profoundly impact neural activity, spatial coding, and synaptic plasticity and learning. What are the sensory mechanisms governing slow oscillations? We hypothesized that the nature of multisensory inputs is a crucial factor in hippocampal rhythmogenesis. We compared the rat hippocampal slow oscillations in the multisensory-rich real world (RW) and in a body-fixed, visual virtual reality (VR). The amplitude and rhythmicity of the hippocampal ~8 Hz theta were enhanced in VR compared to RW. This was accompanied by the emergence of a ~4 Hz oscillation, termed the eta rhythm, evident in the local field potential (LFP) in VR, but not in RW. Similar to theta, eta band amplitude increased with running speed in VR, but not in RW. However, contrary to theta, eta amplitude was highest in the CA1 cell layer, implicating intra-CA1 mechanisms. Consistently, putative CA1 interneurons, but not pyramidal neurons, showed substantially more eta modulation in VR than in RW. These results elucidate the multisensory mechanisms of hippocampal rhythms and the surprising effects of VR on enhancing these rhythms, which has not been achieved pharmacologically and has significant broader implications for VR use in humans. One Sentence SummaryNavigation in virtual reality greatly enhances hippocampal 8Hz theta rhythmicity, and generates a novel, ~4Hz eta rhythm that is localized in the CA1 cell layer and influences interneurons more than pyramidal neurons.

neuroscience↗

Dynamics of Cortical Dendritic Membrane Potential and Spikes in Freely Behaving Rats

Neural activity in vivo is primarily measured using extracellular somatic spikes, which provide limited information about neural computation. Hence, it is necessary to record from neuronal dendrites, which generate dendritic action potentials (DAP) and profoundly influence neural computation and plasticity. We measured neocortical sub- and supra-threshold dendritic membrane potential (DMP) from putative distal-most dendrites using tetrodes in freely behaving rats over multiple days with a high degree of stability and sub-millisecond temporal resolution. DAP firing rates were several fold larger than somatic rates. DAP rates were modulated by subthreshold DMP fluctuations which were far larger than DAP amplitude, indicting hybrid, analog-digital coding in the dendrites. Parietal DAP and DMP exhibited egocentric spatial maps comparable to pyramidal neurons. These results have important implications for neural coding and plasticity.\n\nOne Sentence SummaryMeasurement of cortical dendritic membrane potential for several days in freely behaving rats reveals disproportionate dendritic spiking and analog and digital coding.

neuroscience↗