Biology subjects

Philipsberg, P. A.

Publications and source records attributed to Philipsberg, P. A..

5 recordsLinked to original sources

bioRxiv2025

Medial entorhinal-hippocampal desynchronization parallels the emergence of memory impairment in a mouse model of Alzheimer's disease pathology

Alzheimers disease (AD) is a neurodegenerative disease characterized by progressive impairments in episodic and spatial memory, as well as circuit and network-level dysfunction. While functional impairments in medial entorhinal cortex (MEC) and hippocampus (HPC) have been observed in patients and rodent models of AD, it remains unclear how communication between these regions breaks down in disease, and what specific physiological changes are associated with the onset of memory impairment. We used silicon probes to simultaneously record neural activity in MEC and hippocampus before or after the onset of spatial memory impairment in the 3xTg mouse model of AD pathology. We found that reduced hippocampal theta power, reduced MEC-CA1 theta coherence, and altered phase locking of MEC and hippocampal neurons all coincided with the emergence of spatial memory impairment in 3xTg mice. Together, these findings indicate that disrupted temporal coordination of neural activity in the MEC-hippocampal system parallels the emergence of memory impairment in a model of AD pathology. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=195 SRC="FIGDIR/small/633171v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@11606a5org.highwire.dtl.DTLVardef@10e5d0borg.highwire.dtl.DTLVardef@1feabe1org.highwire.dtl.DTLVardef@c646ed_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGRAPHICAL ABSTRACTC_FLOATNO C_FIG HighlightsO_LISpatial memory impairments in 3xTg mice emerge between 6 and 8 months of age C_LIO_LIMemory deficits emerge alongside reduced HPC theta power and reduced CA1-MEC theta coherence C_LIO_LIMemory deficits emerge alongside disrupted timing of MEC and HPC neural activity C_LIO_LIInterneuron loss in MEC and interneuron desynchronization in HPC occur prior to memory impairment C_LI

neuroscience↗

bioRxiv2024

Simultaneous dual-color calcium imaging in freely-behaving mice

Miniaturized fluorescence microscopes (miniscopes) enable imaging of calcium events from a large population of neurons in freely behaving animals. Traditionally, miniscopes have only been able to record from a single fluorescence wavelength. Here, we present a new open-source dual-channel Miniscope that simultaneously records two wavelengths in freely behaving animals. To enable simultaneous acquisition of two fluorescent wavelengths, we incorporated two CMOS sensors into a single Miniscope. To validate our dual-channel Miniscope, we imaged hippocampal CA1 region that co-expressed a dynamic calcium indicator (GCaMP) and a static nuclear signal (tdTomato) while mice ran on a linear track. Our results suggest that, even when neurons were registered across days using tdTomato signals, hippocampal spatial coding changes over time. In conclusion, our novel dual-channel Miniscope enables imaging of two fluorescence wavelengths with minimal crosstalk between the two channels, opening the doors to a multitude of new experimental possibilities. TeaserNovel open-source dual-channel Miniscope that simultaneously records two wavelengths with minimal crosstalk in freely behaving animals.

neuroscience↗

bioRxiv2024

Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy

Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneous in vivo electrophysiology in hippocampus (HPC) and medial entorhinal cortex (MEC) of control and epileptic mice 3 or 8 weeks after pilocarpine-induced status epilepticus (Pilo-SE). We found that HPC synchronization deficits (including reduced theta power, coherence, and altered interneuron spike timing) emerged within 3 weeks of Pilo-SE, aligning with early-onset, relatively subtle memory deficits. In contrast, abnormal synchronization within MEC and between HPC-MEC emerged later, by 8 weeks after Pilo-SE, when spatial memory impairment was more severe. Furthermore, a distinct subpopulation of MEC layer 3 excitatory neurons (active at theta troughs) was specifically impaired in epileptic mice. Together, these findings suggest that hippocampal-entorhinal circuit dysfunction accumulates and shifts as cognitive impairment progresses in TLE.

neuroscience↗

bioRxiv2023

Chronotate: An open-source tool for manual timestamping and quantification of animal behavior

A core necessity to behavioral neuroscience research is the ability to accurately measure performance on behavioral assays, such as the novel object location and novel object recognition tasks. These tasks are widely used in neuroscience research and measure a rodents instinct for investigating novel features as a proxy to test their memory of a previous experience. Automated tools for scoring behavioral videos can be cost prohibitive and often have difficulty distinguishing between active investigation of an object and simply being in close proximity to an object. As such, many experimenters continue to rely on hand scoring interactions using stopwatches which makes it difficult to review scoring after-the-fact and results in the loss of temporal information. Here, we introduce Chronotate, a free, open-source tool to aid in manually scoring novel object behavior videos. The software consists of an interactive video player with keyboard integration for marking timestamps of behavioral events during video playback, making it simple to quickly score and review bouts of rodent-object interaction. In addition, Chronotate outputs detailed interaction bout data, allowing for nuanced behavioral performance analyses. Using this detailed temporal information, we demonstrate that novel object location performance peaks within the first 3 seconds of interaction time and preference for the novel location becomes reduced across the test session. Thus, Chronotate can be used to determine the temporal structure of interactions on this task and can provide new insight into the memory processes that drive this behavior. Chronotate is available for download at: https://github.com/ShumanLab/Chronotate.

neuroscience↗

bioRxiv2023

Manipulating single-unit theta phase-locking with PhaSER: An open-source tool for real-time phase estimation and manipulation

The precise timing of neuronal spiking relative to the brains endogenous oscillations (i.e., phase-locking or spike-phase coupling) has long been hypothesized to coordinate cognitive processes and maintain excitatory-inhibitory homeostasis. Indeed, disruptions in theta phase-locking have been described in models of neurological diseases with associated cognitive deficits and seizures, such as Alzheimers disease, temporal lobe epilepsy, and autism spectrum disorders. However, due to technical limitations, determining if phase-locking causally contributes to these disease phenotypes has not been possible until recently. To fill this gap and allow for the flexible manipulation of single-unit phase-locking to on-going endogenous oscillations, we developed PhaSER, an open-source tool that allows for phase-specific manipulations. PhaSER can deliver optogenetic stimulation at defined phases of theta in order to shift the preferred firing phase of neurons relative to theta in real-time. Here, we describe and validate this tool in a subpopulation of inhibitory neurons that express somatostatin (SOM) in the CA1 and dentate gyrus (DG) regions of the dorsal hippocampus. We show that PhaSER is able to accurately deliver a photo-manipulation that activates opsin+ SOM neurons at specified phases of theta in real-time in awake, behaving mice. Further, we show that this manipulation is sufficient to alter the preferred firing phase of opsin+ SOM neurons without altering the referenced theta power or phase. All software and hardware requirements to implement real-time phase manipulations during behavior are available online (https://github.com/ShumanLab/PhaSER).

neuroscience↗