Biology subjects

Lindeman, S.

Publications and source records attributed to Lindeman, S..

6 recordsLinked to original sources

bioRxiv2024

Decoding Olfactory Bulb Output: A Behavioral Assessment of Rate, Synchrony, and Respiratory Phase Coding

The olfactory system is a well-known model for studying the temporal encoding of sensory stimuli due to its rhythmic stimulus delivery through respiration. The sniff rhythm is considered critical to structuring the output of computation in the primary olfactory area, the olfactory bulb. Here, Neuropixels recording from awake, head-fixed mice confirmed that both the rate and sniff-locked spike timing are informative about odour identity. We tested the behavioural importance of these temporal features using simple closed-loop optogenetics embedded in custom behavioural paradigms. We found that mice perceive differences in evoked spike counts and discriminate between synchronous vs. asynchronous activations of the output neurons. Surprisingly, they failed to distinguish the timing of evoked activity relative to the sniff cycle. These results challenge the utility of internally generated rhythms as reference signals in the neural encoding of the environment.

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bioRxiv2023

Reward contingency modulates olfactory bulb output via pathway-dependent peri-somatic inhibition

Associating values to environmental cues is a critical aspect of learning from experiences, allowing animals to predict and maximise future rewards. Value-related signals in the brain were once considered a property of higher sensory regions, but its wide distribution across many brain regions is increasingly recognised. Here, we investigate how reward-related signals begin to be incorporated, mechanistically, at the earliest stage of olfactory processing, namely, in the olfactory bulb. In head-fixed mice performing Go/No-Go discrimination of closely related olfactory mixtures, rewarded odours evoke widespread inhibition in one class of output neurons, that is, in mitral cells but not tufted cells. The temporal characteristics of this reward-related inhibition suggest it is odour-driven, but it is also context-dependent since it is absent during pseudo-conditioning and pharmacological silencing of the piriform cortex. Further, the reward-related modulation is present in the somata but not in the apical dendritic tuft of mitral cells, suggesting an involvement of circuit component located deep in the olfactory bulb. Depth-resolved imaging from granule cell dendritic gemmules suggests that granule cells that target mitral cells receive a reward-related extrinsic drive. Our results support the notion that value-related modulation appears at the early stages of sensory processing and provide constraints on long-range and local circuit mechanisms.

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bioRxiv2021

State-dependent linearisation of mixture representations by the olfactory bulb

Sensory systems are often tasked to analyse complex signals from the environment, separating relevant from irrelevant parts. This process of decomposing signals is challenging when a mixture of signals does not equal the sum of its parts, leading to an unpredictable corruption of signal patterns. In olfaction, nonlinear summation is prevalent at various stages of sensory processing. Here, we investigate how the olfactory system deals with binary mixtures of odours under different brain states, using two-photon imaging of olfactory bulb (OB) output neurons. Unlike previous studies using anaesthetised animals, we found that mixture summation is more linear in the early phase of evoked responses in awake, head-fixed mice performing an odour detection task, due to dampened responses. Despite this, and responses being more variable, decoding analyses indicated that the data from behaving mice was well discriminable. Curiously, the time course of decoding accuracy did not correlate strictly with the linearity of summation. Further, a comparison with naive mice indicated that learning to accurately perform the mixture detection task is not accompanied by more linear mixture summation. Finally, using a simulation, we demonstrate that, while saturating sublinearity tends to degrade the discriminability, the extent of the impairment may depend on other factors, including pattern decorrelation. Altogether, our results demonstrate that the mixture representation in the primary olfactory area is state-dependent, but the analytical perception may not strictly correlate with linearity in summation.

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bioRxiv2020

Cerebellar Purkinje cells can differentially modulate coherence between sensory and motor cortex depending on region and behavior

Coherence among sensory and motor cortices is indicative of binding of critical functions in perception, motor planning, action and sleep. Evidence is emerging that the cerebellum can impose coherence between cortical areas, but how and when it does so is unclear. Here, we studied coherence between primary somatosensory (S1) and motor (M1) cortices during sensory stimulation of the whiskers in the presence and absence of optogenetic stimulation of cerebellar Purkinje cells in awake mice. Purkinje cell activation enhanced and reduced sensory-induced S1-M1 coherence in the theta and gamma bands, respectively. This impact only occurred when Purkinje cell stimulation was given simultaneously with sensory stimulation; a 20 ms delay was sufficient to alleviate its impact, suggesting the existence of a fast, cerebellar sensory pathway to S1 and M1. The suppression of gamma band coherence upon Purkinje cell stimulation was significantly stronger during trials with relatively large whisker movements, whereas the theta band changes did not show this correlation. In line with the anatomical distribution of the simple spike and complex spike responses to whisker stimulation, this suppression also occurred following focal stimulation of medial crus 2, but not of lateral crus 1. Granger causality analyses and computational modeling of the involved networks suggest that Purkinje cells control S1-M1 coherence most prominently via the ventrolateral thalamus and M1. Our results indicate that coherences between sensory and motor cortices in different frequency ranges can be dynamically modulated by cerebellar input, and that the modulation depends on the behavioral context and is site-specific. Significance StatementCoherent activity between sensory and motor areas is essential in sensorimotor integration. We show here that the cerebellum can differentially affect cortical theta and gamma band coherences evoked by whisker stimulation via a fast ascending and predictive pathway. In line with the functional heterogeneity of its modular organization, the impact of the cerebellum is region-specific and tuned to ongoing motor responses. These data highlight site-specific and context-dependent interactions between the cerebellum and the cerebral cortex that can come into play during a plethora of sensorimotor functions.

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bioRxiv2018

Aperiodic Rhythms of the Inferior Olive

Inferior olivary activity causes both short-term and long-term changes in cerebellar output underlying motor adaptation and motor learning, respectively. Many of its neurons engage in coherent subthreshold oscillations and are extensively coupled via gap junctions. Studies in reduced preparations suggest that these properties promote rhythmic, synchronized output. However, how these properties interact with synaptic inputs controlling inferior olivary output in intact, awake behaving animals is poorly understood. Here we combine electrophysiological recordings in awake mice with a novel and realistic tissue-scale computational model of the inferior olive to study the relative impact of intrinsic and extrinsic mechanisms governing its activity. Our data and model suggest that oscillations are present in the awake state, but that the period of subthreshold oscillations is variable, resulting in semi-periodic activity, which result in the high unpredictability of sensory-triggered complex spikes occurring in windows of opportunity lasting a few tens of milliseconds. To test the resonant properties of complex spike firing we used different temporal patterns of sensory stimulation in awake mice. Resonance was found to be limited to short intervals no more than a few hundred milliseconds, which could be explained by our network model to be a result of synaptic input to the inferior olive. The model also shows how gap junctional coupling stiffens the olivary network response to sensory modulation of complex spike rhythmicity. Interactions between intrinsic properties and extrinsic inputs can explain short-lasting semi- periodic variations of the spiking rhythms of olivary neurons even though their long-term average firing rate is stable, providing a conceptual framework for the creation of both the short-term and long-term changes in cerebellar output.\n\nAUTHOR SUMMARYActivity of the inferior olive, transmitted via climbing fibers to the cerebellum, regulates initiation and amplitude of movements, signals unexpected sensory feedback, and directs cerebellar learning. It is characterized by widespread subthreshold oscillations and synchronization promoted by strong electrotonic coupling. In brain slices, subthreshold oscillations set a temporal framework determining which inputs can be transmitted by inferior olivary neurons and which will not - dependent on the phase of the oscillation. In our study, we tested whether the subthreshold oscillations had any impact on temporal patterning of climbing fiber activity in intact, awake mice. We did so by recording neural activity of the postsynaptic Purkinje cells, in which complex spike firing faithfully represents climbing fiber activity. For short intervals (<300 ms), we found that many Purkinje cells indeed showed spontaneously rhythmic complex spike activity. However, our experiments designed to evoke resonant responses clearly indicated that complex spikes are not predicated on stimulus history. Our realistic network model of the inferior olive explains the experimental findings via continuous phase modulations of the subthreshold oscillations. We conclude that inferior olivary activity is emerging from an aperiodic rhythm, stabilized by electrotonic coupling, and dependent on the behavioral context transmitted via synaptic input.

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bioRxiv2018

Adaptation of Whisker Movements Requires Cerebellar Potentiation

Cerebellar plasticity underlies motor learning. However, how the cerebellum operates to enable learned changes in motor output is largely unknown. We developed a sensory-driven adaptation protocol for reflexive whisker protraction and recorded Purkinje cell activity from crus 1 and 2 of awake mice. Before training, simple spikes of individual Purkinje cells correlated during reflexive protraction with the whisker position without lead or lag. After training, simple spikes and whisker protractions were both enhanced with the spiking activity now leading the behavioral response. Neuronal and behavior changes did not occur in two cell-specific mouse models with impaired long-term potentiation at parallel fiber to Purkinje cell synapses. Consistent with cerebellar plasticity rules, increased simple spike activity was prominent in cells with low complex spike response probability. Thus, potentiation at parallel fiber to Purkinje cell synapses may contribute to reflex adaptation and enable expression of cerebellar learning through increases in simple spike activity.\n\nImpact statementRomano et al. show that expression of cerebellar whisker learning can be mediated by increases in simple spike activity, depending on LTP induction at parallel fiber to Purkinje cell synapses.

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