Biology subjects

Leutgeb, J. K.

Publications and source records attributed to Leutgeb, J. K..

5 recordsLinked to original sources

bioRxiv2023

Low Rate Hippocampal Delay Period Activity Encodes Behavioral Experience

Remembering what just happened is a crucial prerequisite to form long-term memories but also for establishing and maintaining working memory. So far there is no general agreement about cortical mechanisms that support short-term memory. Using a classifier-based decoding approach, we report that hippocampal activity during few sparsely distributed brief time intervals contains information about the previous sensory motor experience of rodents. These intervals are characterized by only a small increase of firing rate of only a few neurons. These low-rate predictive patterns are present in both working memory and non-working memory tasks, in two rodent species, rats and Mongolian gerbils, are strongly reduced for rats with medial entorhinal cortex lesions, and depend on the familiarity of the sensory-motor context.

neuroscience↗

bioRxiv2022

Localized APP pathology in the hippocampus is sufficient to result in progressive disorganization of the timing of neuronal firing patterns

Deficits in spatial navigation are among the early symptoms in Alzheimers disease patients, consistent with the hippocampal formation as the site for spatial computations and disease onset. Although the correspondence between the early symptoms and brain regions that are affected early in the disease has been recognized, it is not clear whether progressive cognitive decline is solely caused by a spreading pathology or whether a focal pathology can by itself cause aberrant neuronal activity in a larger network. These possibilities cannot be distinguished in standard disease models which broadly express APP across brain regions. We therefore generated a mouse model in which the expression of mutant human APP was limited to hippocampal CA3 cells (CA3-APP mice). We first asked whether the limited pathology in CA3 can result in memory deficits and found impaired performance of CA3-APP mice in a hippocampus-dependent memory task. By then recording in the CA1 region, we asked to what extent neuronal activity patterns emerged in a brain region which received projections from APP-expressing CA3 cells, but did itself not show any primary pathology. While the spatial firing patterns of CA1 cells were preserved, we observed a reduced theta oscillation frequency in the local field potential and in a subpopulation of principal cells in CA1. Furthermore, CA1 interneurons showed decreased theta oscillation frequencies, and this effect was even more pronounced in CA3 interneurons, which also do not directly express APP. Pathology that is highly localized and limited to presynaptic cells is thus sufficient to cause aberrant firing patterns in postsynaptic neuronal networks, which indicates that disease progression is not only from a spreading molecular pathology but also mediated by progressive physiological dysfunction.

neuroscience↗

bioRxiv2022

Distinct roles of dentate gyrus and medial entorhinal cortex inputs for phase precession and temporal correlations in hippocampal CA3 place cells

The hippocampal CA3 subregion is a densely connected recurrent circuit that supports memory consolidation and retrieval by generating and storing sequential neuronal activity patterns that reflect recent experience. While theta phase precession is thought to be critical for generating sequential activity during memory encoding, the circuit mechanisms that support this computation across hippocampal subregions are unknown. By analyzing CA3 network activity in the absence of each of its theta modulated excitatory inputs, we show necessary and unique contributions of the dentate gyrus (DG) and the medial entorhinal cortex (MEC) to phase precession. DG inputs are essential for generating the preferential spiking of CA3 cells during late theta phases and for organizing the temporal order of neuronal firing, while MEC inputs modulate the general precision of phase precession. A computational model that accounts for the empirical findings suggests that DG inputs affect the phase and MEC inputs affect the amplitude of inhibitory subnetworks. Our results thus identify a novel and unique functional role of the DG for the generation of sequence coding in the CA3 recurrent circuit.

neuroscience↗

bioRxiv2021

Theta oscillations in the prefrontal-hippocampal circuit do not couple to respiration-related oscillations

Oscillatory activity is thought to coordinate neural computations across brain regions, and theta oscillations are critical for learning and memory. Because the frequency of respiratory-related oscillations (RROs) in rodents can overlap with the frequency of theta in the prefrontal cortex (PFC) and the hippocampus, we asked whether odor-cued working memory may be supported by coupling between these two oscillations. We first confirmed that RROs are propagated to the hippocampus and PFC and that RRO frequency overlaps with canonical theta frequency. However, we found low coherence between RROs and local theta oscillations in the hippocampus-PFC network when the two types of oscillations overlapped in frequency. This effect was observed during all behavioral phases including during movement and while odors were actively sampled when stationary. Despite the similarity in frequency, RROs and theta oscillations therefore appear to be limited to supporting computation in distinct networks, which suggests that sustained long-range coordination between oscillation patterns that depend on separate pacemakers is not necessary to support at least one type of working memory.

neuroscience↗

bioRxiv2021

Directional Tuning of Phase Precession Properties in the Hippocampus

Running direction in the hippocampus is encoded by rate modulations of place field activity but also by spike timing correlations known as theta sequences. Whether directional rate codes and the directionality of place field correlations are related, however, has so far not been explored and therefore the nature of how directional information is encoded in the cornu ammonis remains unresolved. Here, using a previously published dataset that contains the spike activity of rat hippocampal place cells in the CA1, CA2 and CA3 subregions during free foraging of male Long-Evans rats in a 2D environment, we found that rate and spike timing codes are related. Opposite to a place fields preferred firing rate direction spikes are more likely to undergo theta phase precession and, hence, more strongly impact paired correlations. Furthermore, we identified a subset of field pairs whose theta correlations are intrinsic in that they maintain the same firing order when the running direction is reversed. Both effects are associated with differences in theta phase distributions, and are more prominent in CA3 than CA1. We thus hypothesize that intrinsic spiking is most prominent when the directionally modulated sensory-motor drive of hippocampal firing rates is minimal, suggesting that extrinsic and intrinsic sequences contribute to phase precession as two distinct mechanisms.

neuroscience↗