Explore the vast range of titles available.

Primary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured rat neocortical pyramidal neurons and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to excitatory neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.

Sleep is important for brain plasticity, but its exact function remains mysterious. An influential but controversial idea is that a crucial function of sleep is to drive widespread downscaling of excitatory synaptic strengths. Here, we used real-time sleep classification, ex vivo measurements of postsynaptic strength, and in vivo optogenetic monitoring of thalamocortical synaptic efficacy to ask whether sleep and wake states can constitutively drive changes in synaptic strength within the neocortex of juvenile rats. We found that miniature excitatory postsynaptic current amplitudes onto L4 and L2/3 pyramidal neurons were stable across sleep- and wake-dense epochs in both primary visual (V1) and prefrontal cortex (PFC). Further, chronic monitoring of thalamocortical synaptic efficacy in V1 of freely behaving animals revealed stable responses across even prolonged periods of natural sleep and wake. Together, these data demonstrate that sleep does not drive widespread downscaling of synaptic strengths during the highly plastic critical period in juvenile animals. Whether this remarkable stability across sleep and wake generalizes to the fully mature nervous system remains to be seen.

Brief (2-3d) monocular deprivation (MD) during the critical period induces a profound loss of responsiveness within binocular (V1b) and monocular (V1m) regions of rodent primary visual cortex. This has largely been ascribed to long-term depression (LTD) at thalamocortical synapses, while a contribution from intracortical inhibition has been controversial. Here we used optogenetics to isolate and measure feedforward thalamocortical and feedback intracortical excitation-inhibition (E-I) ratios following brief MD. Despite depression at thalamocortical synapses, thalamocortical E-I ratio was unaffected in V1b and shifted toward excitation in V1m, indicating that thalamocortical excitation was not effectively reduced. In contrast, feedback intracortical E-I ratio was shifted toward inhibition in V1m, and a computational model demonstrated that these opposing shifts produced an overall suppression of layer 4 excitability. Thus, feedforward and feedback E-I ratios can be independently tuned by visual experience, and enhanced feedback inhibition is the primary driving force behind loss of visual responsiveness.

Critical periods are developmental windows of high experience-dependent plasticity essential for the correct refinement of neuronal circuitry and function. While the consequences for the visual system of sensory deprivation during the critical period have been well-characterized, far less is known about the effects of enhanced sensory experience. Here, we use prey capture learning to assess structural and functional plasticity mediating visual learning in the primary visual cortex of critical period mice. We show that prey capture learning improves temporal frequency discrimination and drives a profound remodeling of visual circuitry through an increase in excitatory connectivity and spine turnover. This global and persistent rewiring is not observed in adult hunters and is mediated by TNFα-dependent mechanisms. Our findings demonstrate that enhanced visual experience in a naturalistic paradigm during the critical period can drive structural plasticity to improve visual function, and promotes a long-lasting increase in spine dynamics that could enhance subsequent plasticity.

Neocortical neurons possess stable firing rate set points to which they faithfully return when perturbed. These set points are established early and are stable through adulthood, suggesting they are immutable. Here we challenge this idea using an ethological vision-dependent prey capture learning paradigm in juvenile rats. This learning required visual cortex (V1), and enhanced tuning of V1 neurons to specific behavioral epochs. Chronic recordings revealed a slow, state-dependent increase in V1 firing that began after learning was complete and persisted for days. This upward firing rate plasticity was gradual, gated by wake states, and in L2/3 was driven by a TNFα-dependent increase in excitatory synapses onto pyramidal neurons - all features of homeostatic plasticity within V1. Finally, TNFα inhibition after learning reduced retention of hunting skills. Thus, naturalistic learning in juvenile animals co-opts homeostatic forms of plasticity to reset firing rate setpoints within V1, in a process that facilitates skill consolidation.

ABSTRACT Sleep is important for brain plasticity, but its exact function remains mysterious. An influential but controversial idea is that a crucial function of sleep is to drive widespread downscaling of excitatory synaptic strengths. Here we used real-time sleep classification, ex vivo measurements of postsynaptic strength, and in vivo optogenetic monitoring of thalamocortical synaptic efficacy to ask whether sleep and wake states can constitutively drive changes in synaptic strength within the neocortex of juvenile rats. We found that miniature EPSC amplitudes onto L4 and L2/3 pyramidal neurons were stable across sleep and wake dense epochs in both primary visual (V1) and prefrontal cortex (PFC). Further, chronic monitoring of thalamocortical synaptic efficacy in V1 of freely behaving animals revealed stable responses across even prolonged periods of natural sleep and wake. Together these data demonstrate that neocortical synaptic strengths are remarkably stable across sleep and wake states, and provide strong evidence against the view that sleep drives widespread synaptic downscaling at neocortical synapses. Competing Interest Statement The authors have declared no competing interest. Footnotes * All sections of the paper have been substantially rewritten. * https://github.com/BrianAndCary/papers

Primary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured neocortical pyramidal neurons, and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to excitatory neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses, and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies. Competing Interest Statement The authors have declared no competing interest. Footnotes * Updated text, additional experiments * https://github.com/latereshko/Tereshko_neuron_cilia

Brief (2-3d) monocular deprivation (MD) during the critical period induces a profound loss of responsiveness within layer 4 of primary visual cortex (V1). This has largely been ascribed to long-term depression (LTD) at thalamocortical synapses onto pyramidal neurons, while a contribution from intracortical inhibition has been controversial. Here we used optogenetics to probe feedforward thalamocortical and feedback intracortical excitation-inhibition (E-I) ratios following brief MD. While thalamocortical inputs onto pyramidal neurons were depressed, there was stronger depression onto PV+ interneurons, which shifted the thalamocortical-evoked E-I ratio toward excitation. In contrast, feedback intracortical E-I ratio was shifted toward inhibition, and a computational model of layer 4 demonstrated that these opposing shifts produced an overall suppression of layer 4 excitability. Thus, feedforward and feedback E-I ratios onto the same postsynaptic target can be independently regulated by visual experience, and enhanced feedback inhibition is the primary driving force behind loss of visual responsiveness.

Forkhead transcription factors regulate several important biological processes in many eukaryotic species including fungi. Bioinformatic analysis of the Aspergillus flavus genome revealed four putative forkhead transcription factor genes. Genetic disruption of ( AFLA_005634 ), a homolog of the Aspergillus nidulans fhpA / fkhA gene ( AN4521 ), revealed that the fhpA gene is a negative regulator of both asexual spore production and aflatoxin B 1 production in A. flavus . Furthermore, disruption of the fhpA gene caused a complete loss of sclerotial formation. Overexpression of the fhpA gene caused A. flavus to become more sensitive to sodium chloride whereas disruption of the fhpA gene did not change the ability of A. flavus to respond to any osmotic stress agent tested. Interestingly, both disruption and overexpression of the fhpA gene led to increases in sensitivity to the oxidative stress agent menadione. Overall, these results suggest that fhpA is an important regulator of morphological and chemical development in addition to stress response in A. flavus .

Linear increases in light interception, energy conversion, and partitioning efficiencies have driven past yield gains in soybean. In modern cultivars, canopy light interception and harvest index are reaching theoretical maximum values.