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Lohmann, C.

Publications and source records attributed to Lohmann, C..

6 recordsLinked to original sources

Acetylcholine mediates behavioral state-dependent modulation of spontaneous activity in the developing mouse visual cortex

Synchronized and desynchronized patterns of spontaneous activity during brain development prepare cortical circuits such as the visual cortex for processing external sensory information. Yet the neuromodulatory mechanisms that regulate these early activity patterns remain poorly understood. One such neuromodulator is acetylcholine, which tracks behavioral states and modulates visual cortical activity in adults, but whose function in the developing cortex is largely unexplored. Here, we combined in vivo imaging of genetically encoded acetylcholine and calcium sensors with movement recordings to characterize the relationship between cholinergic dynamics, neuronal activity, and behavioral states in the mouse visual cortex during the second postnatal week, before eye opening. We found that acetylcholine release in the primary visual cortex (V1) closely tracked body movements but was not evoked by visual stimulation alone. Periods of elevated acetylcholine were associated with reduced pairwise neuronal correlations, longer network events with greater temporal jitter, and a transient reduction in mean V1 activity. Chemogenetic inhibition of basal forebrain cholinergic neurons increased the internal synchrony of network events and partially reversed the movement-associated reduction in V1 activity, identifying basal forebrain input as a source of this cholinergic modulation. These findings establish acetylcholine as a state-dependent regulator of spontaneous activity in the developing visual cortex before visual experience begins.

neuroscience↗

Correlated spontaneous activity sets up multi-sensory integration in the developing higher-order cortex

To perceive and navigate complex sensory environments, animals combine sensory information from multiple modalities in specialized brain circuits. Known as multisensory integration, this process typically depends on the existence of co-aligned topographic connections from several sensory areas to downstream circuits exhibiting multimodal representations. How such topographically co-aligned connectivity necessary for multisensory integration gets set up in early stages of development is still unknown. Inspired by the role of spontaneous activity in refining topographic connectivity between early sensory circuits, here we investigated the potential of such spontaneous activity to also guide the co-alignment of multiple sensory modalities in RL, a higher-order associative cortical area rostro-lateral to V1. Analyzing spontaneous activity simultaneously recorded in primary visual and somatosensory cortex and area RL at different developmental ages before sensory experience, we identify candidate features of this activity to guide the emergence of co-aligned topographic multisensory projections with somatosensory leading the visual projection. We confirm this hypothesis using a computational model of activity-dependent circuit refinement, and show that the correlation of spontaneous activity between the visual and somatosensory primary cortex can establish an optimal fraction of multisensory neurons in RL for stimulus decoding. Our model provides an exciting new computational perspective of the role of spontaneous activity in the emergence of topographically co-aligned multimodal sensory representations in downstream circuits, specialized for the processing of rich sensory environments.

neuroscience↗

Clustered synapses develop in distinct dendritic domains in visual cortex before eye opening

Synaptic inputs to cortical neurons are highly structured in adult sensory systems, such that neighboring synapses along dendrites are activated by similar stimuli. This organization of synaptic inputs, called synaptic clustering, is required for high-fidelity signal processing, and clustered synapses can already be observed before eye opening. However, how clustered inputs emerge during development is unknown. Here, we employed concurrent in vivo whole-cell patch clamp and dendritic calcium imaging to map spontaneous synaptic inputs to dendrites of layer 2/3 neurons in the mouse primary visual cortex during the second postnatal week until eye opening. We find that the number of functional synapses and the frequency of transmission events increase several fold during this developmental period. At the beginning of the second postnatal week, synapses assemble specifically in confined dendritic segments, whereas other segments are devoid of synapses. By the end of the second postnatal week, just before eye-opening, dendrites are almost entirely covered by domains of co-active synapses. Finally, co-activity with their neighbor synapses correlates with synaptic stabilization and potentiation. Thus, clustered synapses form in distinct functional domains presumably to equip dendrites with computational modules for high-capacity sensory processing when the eyes open.

neuroscience↗

Adaptation of spontaneous activity in the developing visual cortex

Spontaneous activity drives the establishment of appropriate connectivity in different circuits during brain development. In the mouse primary visual cortex, two distinct patterns of spontaneous activity occur before vision onset: local low-synchronicity events originating in the retina, and global high-synchronicity events originating in the cortex. We sought to determine the contribution of these activity patterns to jointly organize network connectivity through different activity-dependent plasticity rules. We found that local events shape cortical input selectivity and topography, while global events have a homeostatic role regulating connection strength. To generate robust selectivity, we predicted that global events should adapt their amplitude to the history of preceding cortical activation, and confirmed by analyzing in vivo spontaneous cortical activity. This adaptation led to the sparsification of spontaneous activity on a slower timescale during development, demonstrating the remarkable capacity of the developing sensory cortex to acquire sensitivity to visual inputs after eye-opening.

neuroscience↗

Control of spontaneous activity patterns by inhibitory signaling in the developing visual cortex

During early development, even before the senses are active, bursts of activity travel across the nervous system. This spontaneously generated activity drives the refinement of synaptic connections, preparing young networks for patterned sensory input. Synaptic fine-tuning relies not only on the presence of spontaneous activity, but also on the specific characteristics of these activity patterns, such as their frequency, amplitude and synchronicity. Here, we provide evidence that these crucial characteristics are shaped by the relative balance of excitation and inhibition, where patterns with distinct characteristics have different excitatory/inhibitory ratios. Inhibition can control whether cells participate during a spontaneous event, as pharmacogenetic suppression of the somatostatin (SST) expressing subtype of inhibitory interneurons increased cell recruitment and lateral spread of events.

neuroscience↗

Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons

Spontaneous network activity shapes emerging neuronal circuits during early brain development, however how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin powerfully shapes spontaneous activity patterns. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in visual cortex (V1), but not in somatosensory cortex (S1). This differential effect was a consequence of oxytocin only increasing inhibition in V1 and increasing both inhibition and excitation in S1. The increase in inhibition was mediated by the depolarization and increase in excitability of somatostatin+ (SST) interneurons specifically. Accordingly, silencing SST+ neurons pharmacogenetically fully blocked oxytocins effect on inhibition in vitro as well its effect on spontaneous activity patterns in vivo. Thus, oxytocin decreases the excitatory/inhibitory ratio and modulates specific features of V1 spontaneous activity patterns that are crucial for refining developing synaptic connections and sensory processing later in life.

neuroscience↗