Abstract Hippocampal network activity at theta frequencies (5-10Hz) is important for behavior. However, it remains unclear how behaviorally-relevant network theta rhythms arise and interact with cellular dynamics to dictate spike timing. We performed membrane voltage (Vm) imaging of individual CA1 pyramidal cells and parvalbumin interneurons with simultaneous local field potential (LFP) recordings in mice during locomotion. We found that Vm theta rhythms organize spike timing in both cell types regardless of behavioral conditions, but the Vm of parvalbumin interneurons is better synchronized with LFP. The temporal relationships between spikes and LFP theta reliably reflect the Vm-LFP relationships in parvalbumin cells, but not in pyramidal cells. Thus, cellular theta rhythms broadly organize spike timing in CA1 neurons, and parvalbumin interneurons are critical in coordinating network theta rhythms. One-Sentence SummaryCellular membrane voltage of parvalbumin interneurons organizes spiking and network dynamics in the hippocampus.
more »
« less
This content will become publicly available on November 14, 2026
Relative phase of membrane potential theta oscillations between individual hippocampal neurons code space
ABSTRACT The timing of spikes dictates a neuron’s impact on downstream circuits and behavior, and spike timing is determined by the membrane potential (Vm). However, due to technical challenges, it has been impossible to analyze the relative timing of Vm dynamics between neurons during behavior. Using large scale membrane voltage imaging, we simultaneously recorded Vm from many individual hippocampal neurons in animals engaged in a virtual spatial task. We found that relative phase of Vm theta oscillations across neurons exhibit gradual or discrete shifts depending on spatial position. This finding extends beyond previous studies showing Vm dynamics in single neurons or spiking activity in multiple neurons, revealing previously unknown evidence for consistent coding of space by spike-independent relative phase of Vm theta dynamics between neurons.
more »
« less
- Award ID(s):
- 2002971
- PAR ID:
- 10660645
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Deep brain stimulation (DBS) is a promising neuromodulation therapy, but the neurophysiological mechanisms of DBS remain unclear. In awake mice, we performed high-speed membrane voltage fluorescence imaging of individual hippocampal CA1 neurons during DBS delivered at 40 Hz or 140 Hz, free of electrical interference. DBS powerfully depolarized somatic membrane potentials without suppressing spike rate, especially at 140 Hz. Further, DBS paced membrane voltage and spike timing at the stimulation frequency and reduced timed spiking output in response to hippocampal network theta-rhythmic (3–12 Hz) activity patterns. To determine whether DBS directly impacts cellular processing of inputs, we optogenetically evoked theta-rhythmic membrane depolarization at the soma. We found that DBS-evoked membrane depolarization was correlated with DBS-mediated suppression of neuronal responses to optogenetic inputs. These results demonstrate that DBS produces powerful membrane depolarization that interferes with the ability of individual neurons to respond to inputs, creating an informational lesion.more » « less
-
Abstract Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference1,2. However, how cognitive control regulates working memory storage is unclear. Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta–gamma phase–amplitude coupling (TG-PAC). We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality. We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high. By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour. Our results support a multicomponent architecture of working memory1,2, with frontal control managing maintenance of working memory content in storage-related areas3–5. Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.more » « less
-
Abstract Cortical representations supporting many cognitive abilities emerge from underlying circuits comprised of several different cell types. However, cell type-specific contributions to rate and timing-based cortical coding are not well-understood. Here, we investigated the role of parvalbumin neurons in cortical complex scene analysis. Many complex scenes contain sensory stimuli which are highly dynamic in time and compete with stimuli at other spatial locations. Parvalbumin neurons play a fundamental role in balancing excitation and inhibition in cortex and sculpting cortical temporal dynamics; yet their specific role in encoding complex scenes via timing-based coding, and the robustness of temporal representations to spatial competition, has not been investigated. Here, we address these questions in auditory cortex of mice using a cocktail party-like paradigm, integrating electrophysiology, optogenetic manipulations, and a family of spike-distance metrics, to dissect parvalbumin neurons’ contributions towards rate and timing-based coding. We find that suppressing parvalbumin neurons degrades cortical discrimination of dynamic sounds in a cocktail party-like setting via changes in rapid temporal modulations in rate and spike timing, and over a wide range of time-scales. Our findings suggest that parvalbumin neurons play a critical role in enhancing cortical temporal coding and reducing cortical noise, thereby improving representations of dynamic stimuli in complex scenes.more » « less
-
A Relative Spike-Timing Approach to Kernel-Based Decoding Demonstrated for Insect Flight ExperimentsSpike train decoding is considered one of the grand challenges in reverse-engineering neural control systems as well as in the development of neuromorphic controllers. This paper presents a novel relative-time kernel design that accounts for not only individual spike train patterns, but also the relative spike timing between neuron pairs in the population. The new relative-time-kernel-based spike train decoding method proposed in this paper allows us to map the spike trains of a population of neurons onto a lower-dimensional manifold, in which continuous-time trajectories live. The effectiveness of our novel approach is demonstrated by comparing it with existing kernel-based and rate-based decoders, including the traditional reproducing kernel Hilbert space framework. In this paper, we use the data collected in hawk moth flower tracking experiments to test the importance of relative spike timing information for neural control, and focus on the problem of uncovering the mapping from the spike trains of ten primary flight muscles to the resulting forces and torques on the moth body. We show that our new relative-time-kernel-based decoder improves the prediction of the resulting forces and torques by up to 52.1 %. Our proposed relative-time-kernel-based decoder may be used to reverse-engineer neural control systems more accurately by incorporating precise relative spike timing information in spike trains.more » « less
An official website of the United States government
