Dissecting functional connectivity of neuronal microcircuits: experimental and theoretical insights

Feldt, Sarah; Bonifazi, P.; Cossart, Rosa

doi:10.1016/j.tins.2011.02.007

Cited by 172 publications

(165 citation statements)

References 118 publications

(172 reference statements)

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“…At this age, ingrowing cholinergic projections mainly target prelimbic GABAergic neurons. We hypothesize that these CB-positive neurons act as a "hub" organizing the gamma entrainment of local prelimbic networks, as reported previously for developing Hipp (Bonifazi et al, 2009;Feldt et al, 2011). It remains to be elucidated whether the bursting firing of BFn cholinergic neurons or their coupling in oscillatory rhythms represents the main drive for boosting the activity of these GABAergic neurons and, consequently, the prefrontal network activity.…”

Section: Continuous Activity (P14 -P15)supporting

confidence: 57%

Cholinergic Control in Developing Prefrontal–Hippocampal Networks

Janiesch¹,

Krüger²,

Poschel³

et al. 2011

J. Neurosci.

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The cholinergic drive enhances input processing in attentional and mnemonic context by interacting with the activity of prefrontalhippocampal networks. During development, acetylcholine modulates neuronal proliferation, differentiation, and synaptic plasticity, yet its contribution to the maturation of cognitive processing resulting from early entrainment of neuronal networks in oscillatory rhythms remains widely unknown. Here we show that cholinergic projections growing into the rat prefrontal cortex (PFC) toward the end of the first postnatal week boost the generation of nested gamma oscillations superimposed on discontinuous spindle bursts by acting on functional muscarinic but not nicotinic receptors. Although electrical stimulation of cholinergic nuclei increased the occurrence of nested gamma spindle bursts by 41%, diminishment of the cholinergic input by either blockade of the receptors or chronic immunotoxic lesion had the opposite effect. This activation of locally generated gamma episodes by direct cholinergic projections to the PFC was accompanied by indirect modulation of underlying spindle bursts via cholinergic control of hippocampal theta activity. With ongoing maturation and switch of network activity from discontinuous bursts to continuous theta-gamma rhythms, accumulating cholinergic projections acting on both muscarinic and nicotinic receptors mediated the transition from high-amplitude slow to low-amplitude fast rhythms in the PFC. By exerting multiple actions on the oscillatory entrainment of developing prefrontal-hippocampal networks, the cholinergic input may refine them for later gating processing in executive and mnemonic tasks.

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Section: Continuous Activity (P14 -P15)supporting

confidence: 57%

Cholinergic Control in Developing Prefrontal–Hippocampal Networks

Janiesch¹,

Krüger²,

Poschel³

et al. 2011

J. Neurosci.

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“…Correlation index curves showed no difference in the dark and light for both WT and β2KO mice. We next used these correlation indices to construct connectivity maps, which show connections between neurons with the highest correlation indices (26,27). In particular, this strategy has been used in the developing hippocampus to identify highly connected hub neurons, which repeatedly initiate activity (28).…”

Section: Resultsmentioning

confidence: 99%

Intrinsically photosensitive ganglion cells contribute to plasticity in retinal wave circuits

Kirkby

Feller

2013

Proc. Natl. Acad. Sci. U.S.A.

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Correlated spontaneous activity in the developing nervous system is robust to perturbations in the circuits that generate it, suggesting that mechanisms exist to ensure its maintenance. We examine this phenomenon in the developing retina, where blockade of cholinergic circuits that mediate retinal waves during the first postnatal week leads to the generation of "recovered" waves through a distinct, gap junction-mediated circuit. Unlike cholinergic waves, these recovered waves were modulated by dopaminergic and glutamatergic signaling, and required the presence of the gap junction protein connexin 36. Moreover, in contrast to cholinergic waves, recovered waves were stimulated by ambient light via activation of melanopsin-expressing intrinsically photosensitive retinal ganglion cells. The involvement of intrinsically photosensitive retinal ganglion cells in this reconfiguration of wavegenerating circuits offers an avenue of retinal circuit plasticity during development that was previously unknown.retinal development | dopamine | degenerate circuit T he computations performed by neural circuits are not determined by hard-wired anatomy but rather can be altered by experience or different neuromodulatory states (1-3). This plasticity is particularly important during development, when neural circuits show remarkable robustness against perturbations that disrupt the patterned, spontaneous activity required for normal development (4). For example, giant depolarizing potentials in the developing hippocampus are maintained against decreases in gamma-aminobutyric acid (GABAergic) transmission by increasing the strength of glutamatergic transmission (5). Similarly, spontaneous network activity in the developing spinal cord is maintained against alterations in GABAergic transmission by changes in both the intrinsic excitability of individual neurons and changes in synaptic strength of glutamatergic synapses (6). The developing retina also shows robustness against perturbations in circuits that generate spontaneous retinal waves (4). For example, disruption of normal cholinergic transmission during the first postnatal week leads to the generation of waves via a distinct gap junction coupled network (7-9). These observations indicate that degenerate circuit mechanisms exist in the developing retina to maintain spontaneous activity.Here we explore the hypothesis that intrinsically photosensitive retinal ganglion cells (ipRGCs) contribute to this wave circuit plasticity. ipRGCs are a recently discovered class of photoreceptors that express the photopigment melanopsin (10) and are light sensitive in mice from birth, unlike rod and cone photoreceptors, which become photosensitive after 2 postnatal weeks of development (11). Although ipRGCs are typically involved in non-image-forming functions, such as entrainment of circadian rhythms (12), they have been shown to support intraretinal signaling via gap junction coupling and by signaling to dopaminergic amacrine cells (DACs) (13-15). Indeed, light stimulation of ipRGCs can modulate ...

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“…The combination of SC and FC analyses by complex network approaches have led to the conceptualization of brain networks as a connectome 28,29 , and its correlates with age and diseases has gained major attention in fundamental neuroscience 30 . Complex network approaches have highlighted the key role played by several network descriptors in ageing and brain diseases, such as network hubness, hub integrity, network modularity and hierarchical organization of networks.…”

Section: Introductionmentioning

confidence: 99%

What the structural-functional connectome reveals about brain aging: The key role of the fronto-striatal-thalamic circuit and the rejuvenating impact of physical activity

Bonifazi

Erramuzpe

Díez

et al. 2017

Preprint

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Physiological ageing affects brain structure and function impacting its morphology, connectivity and performance. However, at which extent brain-connectivity metrics reflect the age of an individual and whether treatments or lifestyle factors such as physical activity influence the age-connectivity match is still unclear. Here, we assessed the level of physical activity and collected brain images from healthy participants (N=155) ranging from 10 to 80 years to build functional (resting-state) and structural (tractography) connectivity matrices that were combined as connectivity descriptors. Connectivity descriptors were used to compute a maximum likelihood age estimator that was optimized by minimizing the mean absolute error. The connectivity-based estimated age, i.e. the brain-connectome age (BCA), was compared to the chronological age (ChA). Our results were threefold. First, we showed that ageing widely affects the structural-functional connectivity of multiple structures, such as the anterior part of the default mode network, basal ganglia, thalamus, insula, cingulum, hippocampus, parahippocampus, occipital cortex, fusiform, precuneus and temporal pole. Second, our analysis showed that the structure-function connectivity between basal ganglia and thalamus to orbitofrontal and frontal areas make a major contribution to age estimation. Third, we found that high levels of physical activity reduce BCA as compared to ChA, and vice versa, low levels increment it. In conclusion, the BCA model results highlight the impact of physical activity and the key role played by the connectivity between basal ganglia and thalamus to frontal areas on the process of healthy aging. Notably, the same methodology can be generally applied both to evaluate the impact of other factors and therapies on brain ageing, and to identify the structural-functional brain connectivity correlate of other biomarkers than ChA.

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Dissecting functional connectivity of neuronal microcircuits: experimental and theoretical insights

Cited by 172 publications

References 118 publications

Cholinergic Control in Developing Prefrontal–Hippocampal Networks

Cholinergic Control in Developing Prefrontal–Hippocampal Networks

Intrinsically photosensitive ganglion cells contribute to plasticity in retinal wave circuits

What the structural-functional connectome reveals about brain aging: The key role of the fronto-striatal-thalamic circuit and the rejuvenating impact of physical activity

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