Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits.

Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach involves a microscope with an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism. We also introduce a viral transduction method for robust and widespread gene delivery in the mouse brain. These approaches allow us to identify the behavioral state-dependent functional connectivity of pyramidal neurons and vasoactive intestinal peptide-expressing interneurons with long-range cortical networks. Our imaging system provides a powerful strategy for investigating cortical architecture across a wide range of spatial scales

Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression.

The role of remote astrocyte (AC) reaction to central or peripheral axonal insult is not clearly understood. Here we use a transgenic approach to compare the direct influence of normal with diminished AC reactivity on neuronal integrity and synapse recovery following extracranial facial nerve transection in mice. Our model allows straightforward interpretations of AC-neuron signalling by reducing confounding effects imposed by inflammatory cells. We show direct evidence that perineuronal reactive ACs play a major role in maintaining neuronal circuitry following distant axotomy. We reveal a novel function of astrocytic signal transducer and activator of transcription-3 (STAT3). STAT3 regulates perineuronal astrocytic process formation and re-expression of a synaptogenic molecule, thrombospondin-1 (TSP-1), apart from supporting neuronal integrity. We demonstrate that, through this new pathway, TSP-1 is responsible for the remote AC-mediated recovery of excitatory synapses onto axotomized motor neurons in adult mice. These data provide new targets for neuroprotective therapies via optimizing AC-driven plasticity.This is the final version. It was first published in Nature Communications here: http://www.nature.com/ncomms/2014/140711/ncomms5294/abs/ncomms5294.html

SalMotifDB:a tool for analyzing putative transcription factor binding sites in salmonid genomes

publishedVersio

Developmental Participation of VIP Interneurons in Cortical Dynamics

In the mammalian cerebral cortex, local and long-range synaptic connections are believed to relay information related a diverse array of cognitive, emotional, and physiological functions to influence the computations performed by single neurons. While the anatomical connectivity of a single neuron is static on short timescales, its functional involvement in distributed networks may fluctuate rapidly to subserve moment-to-moment changes in behavior. A sparse class of interneurons that express vasoactive intestinal polypeptide (VIP) has been hypothesized to mediate these fluctuations by modulating the gain of cortical micro-circuits in response to neuromodulatory and long-range cortico-cortical inputs. To test this hypothesis, we developed a method to directly measure the functional coupling of individual neurons with distal cortical regions by simultaneous two-photon cellular-resolution and mesoscopic areal-resolution calcium imaging. We used this method to measure how large-scale cortical activity patterns influence the activity of VIP interneurons and their neighboring excitatory neurons, and found that both VIP interneurons and excitatory neurons participate in cortex-wide functional networks that change as a function of behavioral state. Further, we have gained preliminary evidence that the participation of neurons in these networks emerges early in juvenile development and requires both cholinergic and glutamatergic input to VIP interneurons. Efforts are ongoing to better understand the features of large-scale activity patterns that most influence the activity of individual neurons and the mechanisms that couple individual neurons to distributed cortical networks

Balance and gait in older electroconvulsive therapy recipients: a pilot study

Background: Electroconvulsive therapy (ECT) is commonly used to treat depression in older adults. Despite its efficacy in this regard, an associated increase in the risk of falls in this population is a downside of treatment. ECT research has focused on the incidence of falls, but its effect on balance and gait – intrinsic factors in instability and falls – has not been studied. Our aim was to examine changes in balance and gait among older adults before and after a single ECT session and explore the effect of patient-related and treatment factors on any changes found. Methods: Participants were 21 older adults requiring ECT for depression in public psychiatric services. Patients with clinically overt mobility problems (impairing test participation or increasing the risk of falls) were excluded. Balance and gait testing 1 hour pre-ECT and 1, 2 and 3 hours post-ECT included: (1) steady standing test; (2) perturbation of standing balance by self-initiated movements; (3) perturbation of standing balance by an external perturbation; and (4) timed up and go test. Results: No deterioration in test performance was found, using one-way repeated measures analysis of variance. Conclusion: Balance and gait did not deteriorate immediately after ECT. Exclusion of participants with clinically overt mobility problems and falls being better attributable to factors unrelated to balance and gait (such as post-ECT confusion) may account for our findings. This research does not repudiate the occurrence of ECT-related falls but calls into question the utility of introducing routine balance and gait assessment among older ECT recipients without pre-existing mobility problems as a means of preventing them

Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits.

Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach involves a microscope with an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism. We also introduce a viral transduction method for robust and widespread gene delivery in the mouse brain. These approaches allow us to identify the behavioral state-dependent functional connectivity of pyramidal neurons and vasoactive intestinal peptide-expressing interneurons with long-range cortical networks. Our imaging system provides a powerful strategy for investigating cortical architecture across a wide range of spatial scales

Merging species? Evidence for hybridization between the eel parasites <it>Anguillicola crassus</it> and <it>A. novaezelandiae</it> (Nematoda, Anguillicolidea)

<p>Abstract</p> <p>Background</p> <p>The eel parasitic nematodes <it>Anguillicola crassus</it> (originating from Asia) and <it>Anguillicola novaezelandiae</it> (originating from New Zealand) were both introduced to Europe, but occurred in sympatry only in Lake Bracciano in Italy, where they both infected the European eel (<it>Anguilla anguilla</it>). <it>A. novaezelandiae</it> was introduced to the lake in 1975 and disappeared soon after <it>A. crassus</it> was also found there in 1993. We tested the hypothesis if hybridization of the two species might be an explanation for the findings at Lake Bracciano.</p> <p>Findings</p> <p>After laboratory infection of one European eel with 10 third stage larvae of each parasite, two living female and 4 male adults of each species were found to co-occur in the swim bladder after 222 days post exposure. In 9 out of 17 eggs, isolated in total from uteri of the two <it>A. novaezelandiae</it> females, alleles were detected by microsatellite analysis that are characteristic for <it>A. crassus</it>, suggesting the hybrid origin of these eggs. In contrast, none of the eggs isolated from <it>A. crassus</it> females possessed alleles different from those found in <it>A. crassus</it> adults, but it was revealed that one female can be inseminated by several males.</p> <p>Conclusion</p> <p>Our results show that <it>A. crassus</it> and <it>A. novaezelandiae</it> can co-infect a single eel and can mature together in the same swim bladder. We also provide evidence for the possibility of hybridization of <it>A. crassus</it> males with <it>A. novaezelandiae</it> females. Therefore, hybridization might be an explanation for the disappearance of <it>A. novaezelandiae</it> from Lake Bracciano.</p