Biology subjects

Boehringer, R.

Publications and source records attributed to Boehringer, R..

9 recordsLinked to original sources

bioRxiv2025

Category learning disentangles representation of trial events in hippocampus CA1

The hippocampus (HC) is known to encode task-relevant variables, including latent ones, capturing and parsing critical information from sequences into episodes. This is thought to be the basis to form a cognitive map of possible abstract states beyond mere perceptual details, akin a state machine, with predictive value, contributing to an internal world model. However, its specific role in categorization tasks in general, where learning a category may depend on independent, unordered (non-sequential) experienced examples, remains unclear. Here, we investigate CA1 population coding during a categorization paradigm in mice in combination with calcium imaging at different stages of category training with interleaved generalization tests. Our results reveal that hippocampal coding changes critically throughout the different stages of categorization training. Specifically, the disentangling of choice and outcome variables emerges as factorized, abstract, representations and fundamentally distinguishes simple discrimination from categorization training. Furthermore, this factorized geometry relates to improved behavioral performance. Our findings suggest that trial encoding on HC adapts in response to the category structure presented by representing critical events into the appropriate computational format to support generalization of category membership.

neuroscience↗

bioRxiv2025

Activation of latent programs for maternal behavior

Maternal behaviors in mammals, which are critical for offspring survival, involve complex interactions between innate neural circuits and behavioral flexibility. This flexibility depends on environmental needs and external stimuli. Recent studies suggest that social transmission plays a crucial role in the acquisition of maternal behaviors in alloparental (non-maternal) subjects, particularly highlighting visual observation for virgin female mice to acquire pup retrieval behavior. However, the extent to which these behaviors rely on social transmission versus the activation of pre-existing, latent behaviors remains unclear. Here, we systematically investigated the necessity of social observation for maternal behavior acquisition, using a social transmission pup retrieval paradigm in pup-naive virgin female mice. Following the same protocol as previous studies, we compared retrieval performance on conditions that either allowed or prevented the visual observation of maternal demonstrations. Contrary to previous findings reporting substantial differences between these conditions, we found that virgin females readily acquired pup retrieval behavior regardless of their visual access to experienced mothers. We observed no significant correlation between maternal and virgin performance after task exposure. Detailed behavioral analysis revealed that the primary difference between mothers and virgins lay on the latency to initiate the behavior, but once started, virgins complete the retrieval as fast as mothers. Together, our findings show that pup exposure is enough to activate latent behaviors, and suggest that pup retrieval might not be transmitted by visual observation.

animal behavior and cognition↗

bioRxiv2025

Inhibition from the oxytocin system tunes prefrontal circuit dynamics to promote social behavior

The prefrontal cortex (PFC) plays a central role in the selection and expression of diverse social behaviors. A balance of excitation and inhibition is necessary for normal social functioning, but it remains unclear how inhibition sculpts pyramidal activity to promote specific social behaviors. To address this question, we developed a novel decision-making task in which female mice chose between interaction with a male (sociosexual stimulus) or an appetitive non-social option (milk solution). To explore the role of a task-relevant inhibitory subpopulation, we targeted neurons in the medial PFC (mPFC) expressing oxytocin receptors (OXTR neurons). Combining optogenetic inhibition of OXTR neurons with population calcium imaging of pyramidal neural activity, we found that OXTR neurons normally promote interaction with a male compared to a non-social alternative. OXTR neurons also regulate pyramidal activity, which enables a specific ensemble to represent the male option during decision-making. Computational modeling reproduced these findings through a pyramidal competition mechanism, in which regulation by OXTR neurons allows a male-representing pyramidal ensemble to effectively compete against the remaining pyramidal population to drive male choice. These results provide a candidate mechanism by which inhibition enables mPFC pyramidal activity to select for specific social behaviors and may help explain why excitation/inhibition balance is so important for social functioning.

neuroscience↗

bioRxiv2023

Simultaneous single-cell calcium imaging of neuronal population activity and brain-wide BOLD fMRI

Blood Oxygen Level-Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) allows for non-invasive, indirect recordings of neural activity across the whole brain in both humans and animals. However, the relationship between the local neural population activity and the vascular activity is not completely understood. To investigate this relationship, we present a novel MRI compatible single-photon microscope capable of measuring cellular resolution Ca2+ activity of genetically defined neurons during whole-brain BOLD fMRI in awake behaving mice. Using this combined imaging approach, we found a difference in activity patterns between cells which was dependent on their location with respect to the vasculature. Notably, neurons near the vasculature showed pronounced negative activity during contralateral whisker movements at 3 Hz. In a second proof of concept experiment, we demonstrate the potential of recording both local neural activities, like those in the barrel field (SSp-bfd), and BOLD fMRI readings from interlinked brain regions. In sum, the presented technological advancement paves the way for studies examining the interplay between local brain circuits and overarching brain functions. In addition, the new approach enhances our understanding of the vascular BOLD fMRI signal, providing insights into the determinants of local neurovascular functions and the brains organizational framework across various scales.

neuroscience↗

bioRxiv2023

Population-level neural correlates of flexible avoidance learning in medial prefrontal cortex

The medial prefrontal cortex (mPFC) has been proposed to link sensory inputs and behavioral outputs to mediate the execution of learned behaviors. However, how such a link is implemented has remained unclear. To measure prefrontal neural correlates of sensory stimuli and learned behaviors, we performed population calcium imaging during a novel tone-signaled active avoidance paradigm in mice. We developed a novel analysis approach based on dimensionality reduction and decoding that allowed us to identify and isolate population activity patterns related the tone stimulus, learned avoidance actions and general motion. While tone-related activity was not informative about behavior, avoidance-related activity was predictive of upcoming avoidance actions. Moreover, avoidance-related activity distinguished between two different learned avoidance actions, consistent with a model in which mPFC contributes to the selection between different goal-directed actions. Overall, our results suggest that mPFC circuit dynamics transform sensory inputs into specific behavioral outputs through distributed population-level computations.

neuroscience↗

bioRxiv2021

Striatum-projecting prefrontal cortex neurons support working memory maintenance

The medial prefrontal cortex (mPFC) and the dorsomedial striatum (dmStr) are linked to working memory (WM) but how striatum-projecting mPFC neurons contribute to WM encoding, maintenance, or retrieval remains unclear. Here, we probed mPFC[->]dmStr pathway function in freely-moving mice during a T-maze alternation test of spatial WM. Fiber photometry of GCaMP6m-labeled mPFC[->]dmStr projection neurons revealed strongest activity during the delay period that requires WM maintenance. Demonstrating causality, optogenetic inhibition of mPFC[->]dmStr neurons only during the delay period impaired performance. Conversely, enhancing mPFC[->]dmStr pathway activity--via pharmacological suppression of HCN1 or by optogenetic activation during the delay-- alleviated WM impairment induced by NMDA receptor blockade. Consistently, cellular-resolution miniscope imaging resolved preferred activation of >50% mPFC[->]dmStr neurons during WM maintenance. This subpopulation was distinct from neurons showing preference for encoding and retrieval. In all periods, including the delay, neuronal sequences were evident. Striatum-projecting mPFC neurons thus critically contribute to spatial WM maintenance.

neuroscience↗

bioRxiv2020

CA2 inhibition reduces the precision of hippocampal assembly reactivation

The structured reactivation of hippocampal neuronal ensembles during fast synchronous oscillatory events termed sharp-wave ripples (SWRs) has been suggested to play a crucial role in the storage and use of memory. Activity in both the CA2 and CA3 subregions can proceed this population activity in CA1 and chronic inhibition of either region alters SWR oscillations. However, the precise contribution of CA2 to the oscillation, as well as to the reactivation of CA1 neurons within it, remains unclear. Here we employ chemogenetics to transiently silence CA2 pyramidal cells in mice and observe that while SWRs still occur, the reactivation of CA1 pyramidal cell ensembles within the events lose both temporal and informational precision. These observations suggest that CA2 activity contributes to the fidelity of experience-dependent hippocampal replay.

neuroscience↗

bioRxiv2020

Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1

The hippocampus is critical for memory formation. The hypothalamic supramammillary nucleus (SuM) sends long-range projections to hippocampal area CA2. While the SuM-CA2 connection is critical for social memory, how this input acts on the local circuit is unknown. We found that SuM axon stimulation elicited mixed excitatory and inhibitory responses in area CA2 pyramidal neurons (PNs). We found that parvalbumin-expressing basket cells as responsible for the feedforward inhibitory drive of SuM over area CA2. Inhibition recruited by the SuM input onto CA2 PNs increased the precision of action potential firing both in conditions of low and high cholinergic tone. Furthermore, SuM stimulation in area CA2 modulates CA1 activity, indicating that synchronized CA2 output drives a pulsed inhibition in area CA1. Hence, the network revealed here lays basis for understanding how SuM activity directly acts on the local hippocampal circuit to allow social memory encoding.

neuroscience↗

bioRxiv2020

Fast retrograde access to projection neuron circuits underlying vocal learning in songbirds

Understanding the structure and function of neural circuits underlying speech and language is a vital step towards better treatments for diseases of these systems. Songbirds, among the few animal orders that share with humans the ability to learn vocalizations from a conspecific, have provided many insights into the neural mechanisms of vocal development. However, research into vocal learning circuits has been hindered by a lack of tools for rapid genetic targeting of specific neuron populations to meet the quick pace of developmental learning. Here, we present a new viral tool that enables fast and efficient retrograde access to projection neuron populations. In zebra finches, Bengalese finches, canaries, and mice, we demonstrate fast retrograde labeling of cortical or dopaminergic neurons. We further demonstrate the suitability of our construct for detailed morphological analysis, for in vivo imaging of calcium activity, and for multicolor brainbow labeling.

neuroscience↗