Biology subjects

Disterhoft, J. F.

Publications and source records attributed to Disterhoft, J. F..

5 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2024

A universal hippocampal memory code across animals and environments

Learned behaviors often generalize across contexts even though neural representations can vary substantially between environments. How the brain preserves task-relevant information across these changing neural representations remains unclear. This problem is particularly evident in the hippocampus because hippocampal spatial representations reorganize across environments even when learned behaviors generalize successfully. Here, we recorded hippocampal neuronal activity using calcium imaging while rats performed a conditioning task in two distinct environments. Despite remapping of spatial representations, the low-dimensional organization of task related population activity was conserved across contexts, and the temporal relationships among neural population states during task execution were preserved. Strikingly, this relational organization was conserved not only across contexts for individual animals, but also across animals, despite differences in the underlying neural populations and individual experiences. Moreover, this conserved organization was sufficient to support transfer of task decoding across animals, demonstrating that task information could generalize between independently learned neural representations without shared neuron identities. These findings identify a conserved population level neural organization through which the hippocampus can support behavioral generalization despite contextual remapping and suggest that shared organizational neural mechanisms and structures may underlie behavioral generalization across individuals.

neuroscience↗

bioRxiv2021

In Vivo Multi-Day Calcium Imaging of CA1 Hippocampus in Freely Moving Rats Reveals a High Preponderance of Place Cells and No Detectable Photobleaching

Calcium imaging using GCaMP indicators and miniature microscopes has been used to image cellular populations during long timescales and in different task phases, as well as to determine neuronal circuit topology and organization. Because the hippocampus (HPC) is essential for tasks of memory, spatial navigation, and learning, calcium imaging of large populations of HPC neurons can provide new insight on cell changes over time during these tasks. All reported HPC in vivo calcium imaging experiments have been done in mouse. However, rats have many behavioral and physiological experimental advantages over mice. In this paper, we present the first (to our knowledge) in vivo calcium imaging from CA1 hippocampus in freely moving male rats. Using the UCLA Miniscope, we demonstrate that, in rat, hundreds of cells can be visualized and held across weeks. We show that calcium events in these cells are highly correlated with periods of movement, with few calcium events occurring during periods without movement. We additionally show that an extremely large percent of cells recorded during a navigational task are place cells (77.3{+/-}5.0%, surpassing the percent seen during mouse calcium imaging), and that these cells enable accurate decoding of animal position and can be held over days with consistent place fields in a consistent spatial map. A detailed protocol is included, and implications of these advancements on in vivo imaging and place field literature are discussed. Significance statementIn vivo calcium imaging in freely moving animals allows the visualization of cellular activity across days. In this paper, we present the first in vivo Ca2+ recording from CA1 hippocampus in freely moving rats. We demonstrate that hundreds of cells can be visualized and held across weeks, and that calcium activity corresponds to periods of movement. We show that a high percentage (77.3{+/-}5.0%) of imaged cells are place cells, and that these place cells enable accurate decoding and can be held stably over days with little change in field location. Because the hippocampus is essential for many tasks involving memory, navigation, and learning, imaging of large populations of HPC neurons can shed new insight on cellular activity changes and organization.

neuroscience↗

bioRxiv2021

Sex-Dependent Effects of Chronic Microdrive Implantation on Acquisition of Trace Eyeblink Conditioning

Neuroscience techniques, including in vivo recording, have allowed for a great expansion in knowledge; however, this technology may also affect the very phenomena researchers set out to investigate. Including both female and male mice in our associative learning experiments shed light on sex differences on the impact of chronic implantation of tetrodes on learning. While previous research showed intact female mice acquired trace eyeblink conditioning faster than male and ovariectomized females, implantation of chronic microdrive arrays showed sexually dimorphic effects on learning. Microdrive implanted male mice acquired the associative learning paradigm faster than both intact and ovariectomized females. These effects were not due to the weight of the drive alone, as there were no significant sex-differences in learning of animals that received "dummy drive" implants without tetrodes lowered into the brain. Tandem mass tag mass spectrometry and western blot analysis suggest that significant alterations in the MAPK pathway, acute inflammation, and brain derived neurotrophic factor may underlie these observed sex- and surgery-dependent effects on learning.

neuroscience↗

bioRxiv2018

Intrinsic Excitability Increase in Cerebellar Purkinje Cells Following Delay Eyeblink Conditioning in Mice

Cerebellar learning is canonically thought to rely on synaptic plasticity, particularly at synaptic inputs to Purkinje cells. Recently, however, other complementary mechanisms have been identified. Intrinsic plasticity is one such mechanism, and depends in part on the down-regulation of calcium-dependent SK-type K channels, which is associated with an increase in neuronal excitability. In the hippocampus, SK-mediated intrinsic plasticity has been shown to play a role in trace eyeblink conditioning; however, it is not yet known how intrinsic plasticity contributes to a cerebellar learning task such as delay eyeblink conditioning. Whole cell recordings were obtained from acute cerebellar slices from mice ~48 hours after learning a delay eyeblink conditioning task. Over a period of repeated training sessions mice received either distinctly paired trials of a tone co-terminating with a periorbital shock (conditioned mice) or trials in which these stimuli were presented in an unpaired manner (pseudoconditioned mice). Conditioned mice show a significantly reduced afterhyperpolarization (AHP) following trains of parallel fiber stimuli. Moreover, we find that SK-dependent intrinsic plasticity is occluded in conditioned, but not pseudoconditioned mice. These findings show that excitability is enhanced in Purkinje cells after delay eyeblink conditioning and point toward a downregulation of SK channels as a potential underlying mechanism.

neuroscience↗