Yasmin L. Hurd
Oct 16, 2019; 39:8250-8258
Symposium and Mini-Symposium

Krista L. Hyde
Mar 11, 2009; 29:3019-3025
Development Plasticity Repair

Elle M. Murata
Sep 18, 2024; 44:e0573242024-e0573242024
BehavioralSystemsCognitive

Emerging research in nonhuman animals implicates cerebellar projections to the ventral tegmental area (VTA) in appetitive behaviors, but these circuits have not been characterized in humans. Here, we mapped cerebello-VTA white matter connectivity in a cohort of men and women using probabilistic tractography on diffusion imaging data from the Human Connectome Project. We uncovered the topographical organization of these connections by separately tracking from parcels of cerebellar lobule VI, crus I/II, vermis, paravermis, and cerebrocerebellum. Results revealed that connections between the cerebellum and VTA predominantly originate in the right cerebellar hemisphere, interposed nucleus, and paravermal cortex and terminate mostly ipsilaterally. Paravermal crus I sends the most connections to the VTA compared with other lobules. We discovered a mediolateral gradient of connectivity, such that the medial cerebellum has the highest connectivity with the VTA. Individual differences in microstructure were associated with measures of negative affect and social functioning. By splitting the tracts into quarters, we found that the socioaffective effects were driven by the third quarter of the tract, corresponding to the point at which the fibers leave the deep nuclei. Taken together, we produced detailed maps of cerebello-VTA structural connectivity for the first time in humans and established their relevance for trait differences in socioaffective regulation.

Neuronal cytotoxic edema is implicated in neuronal injury and death, yet mitigating brain edema with osmotic and surgical interventions yields poor clinical outcomes. Importantly, neuronal swelling and its downstream consequences during early brain development remain poorly investigated, and new treatment approaches are needed. We explored Ca²⁺-dependent downstream effects after neuronal cytotoxic edema caused by diverse injuries in mice of both sexes using multiphoton Ca²⁺ imaging in vivo [Postnatal Day (P)12–17] and in acute brain slices (P8–12). After different excitotoxic insults, cytosolic GCaMP6s translocated into the nucleus after a few minutes in a subpopulation of neurons, persisting for hours. We used an automated morphology-detection algorithm to detect neuronal soma and quantified the nuclear translocation of GCaMP6s as the nuclear to cytosolic intensity (N/C ratio). Elevated neuronal N/C ratios occurred concurrently with persistent elevation in Ca²⁺ loads and could also occur independently from neuronal swelling. Electron microscopy revealed that the nuclear translocation was associated with the increased nuclear pore size. The nuclear accumulation of GCaMP6s in neurons led to neocortical circuit dysfunction, mitochondrial pathology, and increased cell death. Inhibiting calpains, a family of Ca²⁺-activated proteases, prevented elevated N/C ratios and neuronal swelling. In summary, in the developing brain, we identified a calpain-dependent alteration of nuclear transport in a subpopulation of neurons after disease-relevant insults leading to long-term circuit dysfunction and cell death. The nuclear translocation of GCaMP6 and other cytosolic proteins after acute excitotoxicity can be an early biomarker of brain injury in the developing brain.

Human sleep exhibits multiple, recurrent temporal regularities, ranging from circadian rhythms to sleep stage cycles and neuronal oscillations during nonrapid eye movement sleep. Moreover, recent evidence revealed a functional role of aperiodic activity, which reliably discriminates different sleep stages. Aperiodic activity is commonly defined as the spectral slope of the 1/frequency (1/f) decay function of the electrophysiological power spectrum. However, several lines of inquiry now indicate that the aperiodic component of the power spectrum might be better characterized by a superposition of several decay processes with associated timescales. Here, we determined multiple timescales, which jointly shape aperiodic activity using human intracranial electroencephalography. Across three independent studies (47 participants, 23 female), our results reveal that aperiodic activity reliably dissociated sleep stage-dependent dynamics in a regionally specific manner. A principled approach to parametrize aperiodic activity delineated several, spatially and state-specific timescales. Lastly, we employed pharmacological modulation by means of propofol anesthesia to disentangle state-invariant timescales that may reflect physical properties of the underlying neural population from state-specific timescales that likely constitute functional interactions. Collectively, these results establish the presence of multiple intrinsic timescales that define the electrophysiological power spectrum during distinct brain states.

We used virus-mediated anterograde and retrograde tracing, optogenetic modulation, immunostaining, in situ hybridization, and patch-clamp recordings in acute brain slices to study the release mechanism and μ-opioid modulation of the dual glutamatergic/GABAergic inputs from the ventral tegmental area and supramammillary nucleus to the granule cells of the dorsal hippocampus of male and female mice. In keeping with previous reports showing that the two transmitters are released by separate active zones within the same terminals, we found that the short-term plasticity and pharmacological modulation of the glutamatergic and GABAergic currents are indistinguishable. We further found that glutamate and GABA release at these synapses are both virtually completely mediated by N- and P/Q-type calcium channels. We then investigated μ-opioid modulation of these synapses and found that activation of μ-opioid receptors (MORs) strongly inhibits the glutamate and GABA release, mostly through inhibition of presynaptic N-type channels. However, the modulation by MORs of these dual synapses is complex, as it likely includes also a disinhibition due to downmodulation of local GABAergic interneurons which make direct axo-axonic contacts with the dual glutamatergic/GABAergic terminals. We discuss how this opioid modulation may enhance LTP at the perforant path inputs, potentially contributing to reinforce memories of drug-associated contexts.

Sleep is known to drive the consolidation of motor memories. During nonrapid eye movement (NREM) sleep, the close temporal proximity between slow oscillations (SOs) and spindles ("nesting" of SO-spindles) is known to be essential for consolidation, likely because it is closely associated with the reactivation of awake task activity. Interestingly, recent work has found that spindles can occur in temporal clusters or "trains." However, it remains unclear how spindle trains are related to the nesting phenomenon. Here, we hypothesized that spindle trains are more likely when SOs co-occur in the prefrontal and motor cortex. We conducted simultaneous neural recordings in the medial prefrontal cortex (mPFC) and primary motor cortex (M1) of male rats training on the reach-to-grasp motor task. We found that intracortically recorded M1 spindles are organized into distinct temporal clusters. Notably, the occurrence of temporally precise SOs between mPFC and M1 was a strong predictor of spindle trains. Moreover, reactivation of awake task patterns is much more persistent during spindle trains in comparison with that during isolated spindles. Together, our work suggests that the precise coupling of SOs across mPFC and M1 may be a potential driver of spindle trains and persistent reactivation of motor memory during NREM sleep.

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here, we report that bilirubin (BIL)-dependent cell death in the auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated current (I_h), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca²⁺-dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, I_h, and death, compromising audition at the young adult stage in HCN1^+/+, but not in HCN1^–/– genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca²⁺ overload, neuronal death, and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy.

Team on ground regrouped; strengthened with surge personnel; Declaration of corporate scale-up response

by Qu Dongyu, Director-General of the Food and Agriculture Organization of the United Nations (FAO).

Information Note.

FAO’s responses to the crisis in Ukraine and its impacts on global food security: data analyses, policy recommendations, and actions on the ground.

The Liège-Guillemins railway station looks like it belongs far in the future: a vast curving monolith of glass, steel and concrete curves extending high above the train tracks. Just as astonishing as its design is the fact that it was built while the normal train schedules continued, with no disruption.

A new study identified the tiny pollutants in the olfactory bulbs of eight cadavers, suggesting microplastics can travel through the nose to the brain

The brain diagram, called a connectome, could revolutionize researchers' understanding of the human brain, which has many parallels with a fruit fly's

A $1 million grant from the U.S. is the latest effort to support Ukraine's fight to preserve its rich past

Scientists used EEG headsets, MRI machines and eye trackers to study volunteers' responses to five paintings housed at the Mauritshuis museum in the Netherlands

You asked, we answered

Kate MacEachern is a Canadian veteran from Ballantynes Cove, N.S., but her service years are far from over. She has spent about two years living in Ukraine, delivering humanitarian aid to communities across the country.

Genetically encoded calcium indicators (GECIs) allow for the noninvasive evaluation of neuronal activity in vivo, and imaging GECIs in Drosophila has become commonplace for understanding neural functions and connectivity in this system. GECIs can also be used as read-outs for studying sleep in this model organism. Here, we describe a methodology for tracking the activity of neurons in the fly brain using a two-photon (2p) microscopy system. This method can be adapted to perform functional studies of neural activity in Drosophila under both spontaneous and evoked conditions, as well as during spontaneous or induced sleep. We first describe a tethering and surgical procedure that allows survival under the microscopy conditions required for long-term recordings. We then outline the steps and reagents required for optogenetic activation of sleep-promoting neurons while simultaneously recording neural activity from the fly brain. We also describe the procedure for recording from two different locations—namely, the top of the head (e.g., to record mushroom body calyx activity) or the back of the head (e.g., to record central complex activity). We also provide different strategies for recording from GECIs confined to the cell body versus the entire neuron. Finally, we describe the steps required for analyzing the multidimensional data that can be acquired. In all, this protocol shows how to perform calcium imaging experiments in tethered flies, with a focus on acquiring spontaneous and induced sleep data.

Sleep studies in Drosophila melanogaster rely mostly on behavioral read-outs to support molecular or circuit-level investigations in this model. Electrophysiology can provide an additional level of understanding in these studies to, for example, investigate changes in brain activity associated with sleep manipulations. In this protocol, we describe a procedure for performing multichannel local field potential (LFP) recordings in the fruit fly, with a flexible system that can be adapted to different experimental paradigms and situations. The approach uses electrodes containing multiple recording sites (16), allowing the acquisition of large amounts of neuronal activity data from a transect through the brain while flies are still able to sleep. The approach starts by tethering the fly, followed by positioning it on an air-supported ball. A multichannel silicon probe is then inserted laterally into the fly brain via one eye, allowing for recording of electrical signals from the retina through to the central brain. These recordings can be acquired under spontaneous conditions or in the presence of visual stimuli, and the minimal surgery promotes long-term recordings (e.g., overnight). Sleep and wake can be tracked using infrared cameras, which allow for the measurement of locomotive activity as well as microbehaviors such as proboscis extensions during sleep. The protocol has been optimized to promote subject survivability, which is an important factor when performing long-term (~16-h) recordings. The approach described here uses specific recording probes, data acquisition devices, and analysis tools. Although it is expected that some of these items might need to be adapted to the equipment available in different laboratories, the overall aim is to provide an overview on how to record electrical activity across the brain of behaving (and sleeping) flies using this kind of approach and technology.

StandardAero says new funding from the provincial and federal governments will help expand its Winnipeg operations by training more specialized technicians, managers, support personnel and engineers.

Officials have issued wind and rainfall warnings for Tuesday night in several regions as another fall storm approaches southwestern B.C.

Ukraine attacked Moscow on Sunday with at least 34 drones, the biggest drone strike on the Russian capital since the start of the war in 2022, forcing flights to be diverted from three of the city's major airports and injuring at least one person.

U.S. president-elect Donald Trump spoke with Russian President Vladimir Putin and advised him not to escalate the Ukraine war, a source familiar with the conversation said, but the Kremlin denied the two had spoken.

A federal judge sentenced a Massachusetts Air National Guard member to 15 years in prison Tuesday for leaking classified military documents about the war in Ukraine, actions prosecutors said put the country's national security at risk, endangered other military members and damaged U.S. relationships with its allies.

Macroeconomic risks for grains and oilseeds include China's growth and FX rates.

Some Ukrainians living in Calgary say they're even more worried for their friends and family back home in light of Donald Trump's election win.

A researcher may have many reasons for wanting to establish new laboratory colonies from field-collected mosquitoes. In particular, the ability to study the diversity found within and among natural populations in a controlled laboratory environment opens up a wide range of possibilities for understanding how and why burdens of vector-borne disease vary over space and time. However, field-collected mosquitoes are often more difficult to work with than established laboratory strains, and considerable logistical challenges are involved in safely transporting field-collected mosquitoes into the laboratory. Here, we provide advice for researchers working with Aedes aegypti, Anopheles gambiae, and Culex pipiens, as well as notes on other closely related species. We provide guidance on each stage of the life cycle and highlight the life stages for which it is easiest to initiate new laboratory colonies for each species. In accompanying protocols, we provide methods detailing Ae. aegypti egg collection and hatching as well as how to transport larvae and pupae from the field.

Sleep is likely a whole-brain phenomenon, with most of the brain probably benefiting from this state of decreased arousal. Recent advances in our understanding of some potential sleep functions, such as metabolite clearance and synaptic homeostasis, make it evident why the whole brain is likely impacted by sleep: All neurons have synapses, and all neurons produce waste metabolites. Sleep experiments in the fly Drosophila melanogaster suggest that diverse sleep functions appear to be conserved across all animals. Studies of brain activity during sleep in humans typically involve multidimensional data sets, such as those acquired by electroencephalograms (EEGs) or functional magnetic resonance imaging (fMRI), and these whole-brain read-outs often reveal important qualities of different sleep stages, such as changes in frequency dynamics or connectivity. Recently, various techniques have been developed that allow for the recording of neural activity simultaneously across multiple regions of the fly brain. These whole-brain-recording approaches will be important for better understanding sleep physiology and function, as they provide a more comprehensive view of neural dynamics during sleep and wake in a relevant model system. Here, we present a brief summary of some of the findings derived from sleep activity recording studies in sleeping Drosophila flies and discuss the value of electrophysiological versus calcium imaging techniques. Although these involve very different preparations, they both highlight the value of multidimensional data for studying sleep in this model system, like the use of both EEG and fMRI in humans.

Quick design turnaround and easy documentation process help UK-based company move products to market faster

North American door control system leader's engineering work is critical for passenger safety

3D mechanical design and analysis software dramatically increases productivity and reduces revision for precision optical manufacturer

Virginia McGathey, www.VirginiaMcGathey.com

Virginia McGathey, www.VirginiaMcGathey.com

Scott Shellady, TJM Investments

Virginia McGathey, www.VirginiaMcGathey.com

Scott Shellady, TJM Investments

Virginia McGathey, www.VirginiaMcGathey.com

Virginia McGathey, www.VirginiaMcGathey.com

OM's International Intensive School of Missions in Panama is getting ready to start in January 2012 to equip Latinos for missions.

Through training at OM, Rebecca became more confident sharing Jesus in her home country.

After a week of heavy rains in Central America, the area is left in tragedy. OM Guatemala is desperate to help.

Extreme Leadership Training camps create unity in Ukraine.

OM Ukraine's sports team equips and trains churches in using non-traditional sports in their summer camps.

A Ukrainian pastor responds to nearly 100 per cent unemployment in his village by starting biofuel and cash crop business enterprises.

Through a new cricket league and sports field approved by the local government, OM Ukraine can minister to hundreds of local families.

Ministering in a country at war is not fun – but a privilege. Ukraine is going through intense emotions and people are open to Kingdom conversations.