Biology subjects

Draguhn, A.

Publications and source records attributed to Draguhn, A..

7 recordsLinked to original sources

bioRxiv2024

A tactile discrimination task to study neuronal dynamics in freely-moving mice

Sensory discrimination tasks are valuable tools to study neuronal mechanisms of perception and learning. Most discrimination tasks for electrophysiological and imaging studies in rodents require the animals to be head-fixed. However, implementing neurophysiological recordings into more ethologically realistic settings with unrestrained animals has been challenging. Here, we introduce a whisker-dependent discrimination task for freely moving mice, integrating electrophysiology and calcium imaging with cellular resolution. In this go/no-go paradigm, male mice learned to discriminate aperture widths within days while foraging on a linear platform. The setups versatility enables exploration into diverse behavioral aspects, including tactile discrimination thresholds, valence-dependent behavior, and cognitive flexibility following repeated task rule reversals. Rule learning was highly stereotypical, fast and reproducible across individual mice. Electrophysiological recordings revealed distributed tactile processing across the thalamocortical system, with subsets of units encoding both movement- and stimulus-related features. Sensory encoding was strongly modulated by behavioral state, with neurons tuned to locomotion, whisking, whisker angle and phase, head angle, and spatial position. By enabling simultaneous extracellular recordings and calcium imaging within the same freely moving paradigm, this approach allows for precise synchronization of neural activity with multiple behavioral readouts. This paradigm provides a versatile tool to elucidate neural mechanisms of cognition and sensory processing in naturalistic conditions.

neuroscience↗

bioRxiv2023

Regulation of hippocampal mossy fiber-CA3 synapse function by a Bcl11b/C1ql2/Nrxn3(25b+) pathway

The transcription factor Bcl11b has been linked to neurodevelopmental and neuropsychiatric disorders associated with synaptic dysfunction. Bcl11b is highly expressed in dentate gyrus granule neurons and is required for the structural and functional integrity of mossy fiber-CA3 synapses. The underlying molecular mechanisms, however, remained unclear. We show that the synaptic organizer molecule C1ql2 is a direct functional target of Bcl11b that regulates synaptic vesicle recruitment and long-term potentiation at mossy fiber-CA3 synapses in vivo and in vitro. Furthermore, we demonstrate C1ql2 to exert its functions through direct interaction with a specific splice variant of neurexin-3, Nrxn3(25b+). Interruption of C1ql2-Nrxn3(25b+) interaction by expression of a non-binding C1ql2 mutant or by deletion of Nrxn3 in the dentate gyrus granule neurons recapitulates major parts of the Bcl11b as well as C1ql2 mutant phenotype. Together, this study identifies a novel C1ql2-Nrxn3(25b+)-dependent signaling pathway through which Bcl11b controls mossy fiber-CA3 synapse function. Thus, our findings contribute to the mechanistic understanding of neurodevelopmental disorders accompanied by synaptic dysfunction.

neuroscience↗

bioRxiv2022

Hippocampal-medial entorhinal circuit is differently organized along the dorsoventral axis in rodents

The general understanding of hippocampal circuits is that the hippocampus and the entorhinal cortex (EC) are topographically connected through parallel identical circuits along the dorsoventral axis. Our anterograde tracing and in vitro electrophysiology data, however, show a markedly different dorsoventral organization of the hippocampal projection to the medial EC (MEC). Whereas dorsal hippocampal projections are confined to the dorsal MEC and preferentially target layer Vb (LVb) over layer Va (LVa) neurons, the ventral hippocampus innervates the entire dorsoventral extent of MEC. In the ventral MEC, these projections innervate neurons in both LVa and LVb. In contrast, in the dorsal MEC, ventral hippocampal projections target mainly LVa neurons. As LVa neurons project to telencephalic structures, our findings indicate that the ventral hippocampus regulates LVa-mediated entorhinal-neocortical output from both the dorsal and ventral MEC. Overall, the marked dorsoventral differences in hippocampal-entorhinal connectivity impose important constraints on signal flow in hippocampal-neocortical circuits.

neuroscience↗

bioRxiv2020

Causal relations between cortical network oscillations and breathing frequency

Nasal breathing generates a rhythmic signal which entrains cortical network oscillations in widespread brain regions on a cycle-to-cycle time scale. It is unknown, however, how respiration and neuronal network activity interact on a larger time scale: are breathing frequency and typical neuronal oscillation patterns correlated? Is there any directionality or causal relationship? To address these questions, we recorded field potentials from the posterior parietal cortex of mice together with respiration during REM sleep. In this state, the parietal cortex exhibits prominent theta and gamma oscillations while behavioral activity is minimal, reducing confounding signals. We found that the instantaneous breathing rate strongly correlates with the instantaneous frequency and amplitude of both theta and gamma oscillations. Granger causality analysis revealed specific directionalities for different rhythms: changes in theta activity precede and cause changes in breathing rate, suggesting control of breathing frequency by the functional state of the brain. On the other hand, the instantaneous breathing rate Granger-causes changes in gamma oscillations, suggesting that gamma is influenced by a peripheral reafference signal. These findings show that breathing causally relates to different patterns of rhythmic brain activity, revealing new and complex interactions between elementary physiological functions and neuronal information processing. Significance StatementThe study of the interactions between respiration and brain activity has been focused on phase-entrainment relations, in which cortical networks oscillate phase-locked to breathing cycles. Here we discovered new and much broader interactions which link respiration rate (frequency) to different patterns of oscillatory brain activity. Specifically, we show that the instantaneous breathing rate strongly correlates with the instantaneous frequency and amplitude of theta and gamma oscillations, two major network patterns associated with cognitive functions. Interestingly, causality analyses reveal that changes in breathing rate follow theta, suggesting a central drive, while in contrast, gamma activity follows changes in breathing rate, suggesting the role of a reafferent signal. Our results reveal new mechanisms by which nasal breathing patterns may influence brain functions.

neuroscience↗

bioRxiv2020

Theta-gamma coupling depends on breathing rate

Temporal coupling between theta and gamma oscillations is a hallmark activity pattern of several cortical networks and becomes especially prominent during REM sleep. In a parallel approach, nasal breathing has been recently shown to generate phase-entrained network oscillations which also modulate gamma. Both slow rhythms (theta and respiration-entrained oscillations) have been suggested to aid large-scale integration but they differ in frequency, display low coherence, and modulate different gamma sub-bands. Respiration and theta are therefore believed to be largely independent. In the present work, however, we report an unexpected but robust relation between theta-gamma coupling and respiration in mice. Interestingly, this relation takes place not through the phase of individual respiration cycles, but through respiration rate: the strength of theta-gamma coupling exhibits an inverted V-shaped dependence on breathing rate, leading to maximal coupling at breathing frequencies of 4-6 Hz. Noteworthy, when subdividing sleep epochs into phasic and tonic REM patterns, we find that breathing differentially relates to theta-gamma coupling in each state, providing new evidence for their physiological distinctiveness. Altogether, our results reveal that breathing correlates with brain activity not only through phase-entrainment but also through rate-dependent relations with theta-gamma coupling. Thus, the link between respiration and other patterns of cortical network activity is more complex than previously assumed.

neuroscience↗

bioRxiv2019

Respiration competes with theta for modulating parietal cortex neurons

Recent work has shown that nasal respiration entrains local field potential (LFP) and neuronal activity in widespread regions of the brain. This includes non-olfactory regions where respiration-coupled oscillations have been described in different mammals, such as rodents, cats and humans. They may, thus, constitute a global signal aiding interregional communication. Nevertheless, the brain produces other widespread slow rhythms, such as theta oscillations, which also mediate long-range synchronization of neuronal activity. It is completely unknown how these different signals interact to control neuronal network activity. In this work, we characterized respiration- and theta-coupled activity in the posterior parietal cortex of mice. Our results show that respiration-coupled and theta oscillations have different laminar profiles, in which respiration preferentially entrains LFPs and units in more superficial layers, whereas theta modulation does not differ across the parietal cortex. Interestingly, we find that the percentage of theta-modulated units increases in the absence of respiration-coupled oscillations, suggesting that both rhythms compete for modulating parietal cortex neurons. We further show through intracellular recordings that synaptic inhibition is likely to play a role in generating respiration-coupled oscillations at the membrane potential level. Finally, we provide anatomical and electrophysiological evidence of reciprocal monosynaptic connections between the anterior cingulate and posterior parietal cortices, suggesting a possible source of respiration-coupled activity in the parietal cortex.

neuroscience↗

bioRxiv2017

Parallel Occurrence Of Theta And Respiration-Coupled Network Oscillations Throughout The Mouse Brain

Slow brain oscillations are usually coherent over long distances and are thought to constitute a means to link distributed cell assemblies. In mice, theta oscillations (4-12 Hz) stand as one of the most studied global slow rhythms. Previous research has suggested that theta takes part in interregional communication required for cognitive functions. However, mice often breathe at theta frequency, and we have recently reported that nasal respiration leads to synchronous network oscillations that are independent of theta. Namely, we showed that respiration-coupled oscillations occur in the hippocampus, prelimbic cortex, and parietal cortex, suggesting that, as theta, respiration-coupled oscillations are also global. In the present work, we sought to extend these findings by tracking respiration while simultaneously recording local field potentials from 15 brain regions of freely moving mice during exploration and REM sleep. We report that respiration-coupled rhythms can be detected in parallel with theta in widespread neocortical regions, from prefrontal to visual areas, and also in subcortical structures such as the thalamus, amygdala and ventral hippocampus. Though both rhythms occur simultaneously, respiration-coupled oscillations are more dominant in frontal regions while theta oscillations prevail in more caudal networks. We conclude that respiration-coupled oscillations are a global brain rhythm suited to entrain distributed networks into a common regime. This pattern might have escaped attention in previous studies due to the absence of respiration monitoring, its similarity with theta oscillations, and its highly variable peak frequency. It should, however, be considered as a widespread signal and potential mechanism of long-range network communication.

neuroscience↗