An ultra-short-acting benzodiazepine in thalamic nucleus reuniens undermines fear extinction via intermediation of hippocamposeptal circuits

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 7, 2024

Abstract Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, we reveal its impact on thalamic nucleus reuniens (RE) interconnected hippocamposeptal circuits during extinction. Systemic or RE-specific administration of remimazolam impedes extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, compromised projects ventral hippocampus (vHPC), which in turn sends projections characterized feed-forward neurons LS. This is coupled with LS collectively constituting overall positive feedback construct that promotes negates facilitation disrupting this circuit. Thus, disrupts caused intermediation, offering mechanistic insights dilemma combining anxiolytics extinction-based exposure therapy.

Язык: Английский

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A preprocessing toolbox for 2-photon subcellular calcium imaging

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 5, 2024

ABSTRACT Recording the spiking activity from subcellular compartments of neurons such as axons and dendrites during behavior with 2-photon calcium imaging is increasingly common yet remains challenging due to low signal-to-noise, inaccurate region-of-interest (ROI) identification, movement artifacts, difficulty in grouping ROIs same neuron. To address these issues, we present a computationally efficient pre-processing pipeline for signal detection, artifact ROI grouping. For capture frequency profile transient dynamics by applying Fast Fourier Transform (FFT) on smoothed time-series traces collected axon ROIs. We then apply band-pass filtering methods (e.g. 0.05 0.12 Hz) select that contain frequencies match power band transients. remove motion artifacts z-plane movement, Principal Component Analysis all use Bottom-Up Segmentation change-point detection model first principal component. After removing further identify transients noise analyzing their prominence duration. Finally, high correlation are grouped using hierarchical or k-means clustering. Using CA1 region, confirm both clustering effectively determine optimal number clusters pairwise matrices, yielding similar groupings “ground truth” data. Our approach provides guideline standardizing extraction physiological signals imaging.

Язык: Английский

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Projections from thalamic nucleus reuniens to hippocampal CA1 area participate in context fear extinction by affecting extinction-induced molecular remodeling of excitatory synapses

eLife, Год журнала: 2024, Номер unknown

Опубликована: Окт. 8, 2024

The ability to extinguish contextual fear in a changing environment is crucial for animal survival. Recent data support the role of thalamic nucleus reuniens (RE) and its projections dorsal hippocampal CA1 area (RE→dCA1) this process. However, it remains poorly understood how RE impacts dCA1 neurons during extinction (CFE). Here, we reveal that RE→dCA1 pathway contributes by affecting CFE-induced molecular remodeling excitatory synapses. Anatomical tracing chemogenetic manipulation mice demonstrate form synapses regulate synaptic transmission stratum oriens (SO) lacunosum-moleculare (SLM) area, but not radiatum (SR). We also observe CFE-specific structural changes expression scaffold protein, PSD-95, both strata innervated RE, SR. Interestingly, only SLM are specific dendrites RE. To further projection CFE, brief inhibition CFE session persistently impairs formation memory PSD-95 levels SLM. Thus, our indicate participates regulating

Язык: Английский

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Projections from thalamic nucleus reuniens to hippocampal CA1 area participate in context fear extinction by affecting extinction-induced molecular remodeling of excitatory synapses

Опубликована: Окт. 8, 2024

The ability to extinguish contextual fear in a changing environment is crucial for animal survival. Recent data support the role of thalamic nucleus reuniens (RE) and its projections dorsal hippocampal CA1 area (RE→dCA1) this process. However, it remains poorly understood how RE impacts dCA1 neurons during extinction (CFE). Here, we reveal that RE→dCA1 pathway contributes consolidation CFE memory by affecting CFE-induced molecular remodeling excitatory synapses. Anatomical tracing chemogenetic manipulation mice demonstrate form synapses regulate synaptic transmission stratum oriens (SO) lacunosum-moleculare (SLM) area, but not radiatum (SR). We also observe CFE-specific structural changes expression scaffold protein, PSD-95, both strata innervated RE, SR. Interestingly, only SLM are specific dendrites RE. To further projection CFE, brief inhibition session persistently impairs formation PSD-95 levels SLM. Thus, our indicate participates regulating

Язык: Английский

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A contextual fear conditioning paradigm in head-fixed mice exploring virtual reality.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 27, 2024

ABSTRACT Contextual fear conditioning is a classical laboratory task that tests associative memory formation and recall. Techniques such as multi-photon microscopy holographic stimulation offer tremendous opportunities to understand the neural underpinnings of these memories. However, techniques generally require animals be head-fixed. There are few paradigms test contextual in head-fixed mice, none where behavioral outcome following freezing, most common measure freely moving animals. To address this gap, we developed paradigm mice using virtual reality (VR) environments. We designed an apparatus deliver tail shocks (unconditioned stimulus, US) while navigated VR environment (conditioned CS). The acquisition was tested when were reintroduced shock-paired day. three different variations and, all them, observed increased conditioned response characterized by freezing behavior. This especially prominent during first trial environment, compared neutral received no shocks. Our results demonstrate can VR, discriminate between feared context, display response, similar behaving Furthermore, two-photon microscope, imaged from large populations hippocampal CA1 neurons before, during, conditioning. findings reconfirmed those literature on animals, showing place cells undergo remapping show narrower fields approach offers new study mechanisms underlying formation, recall, extinction As preparation compatible with stimulation, it enables long-term tracking manipulation throughout distinct stages provides subcellular resolution for investigating axonal, dendritic, synaptic dynamics real-time.

Язык: Английский

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