The state’s supreme court ended a yearslong fight over K-12 funding earlier this summer, but in districts across the state the battles have continued and tensions remain.

Georgia football tumbled nine spots in the College Football Playoff rankings Tuesday and fell out of the 12-team bracket. What committee chair said

Many schools that have recently opened their doors are already seeing COVID-19 cases among students and staff. Should that shake the confidence of other school leaders who are planning to reopen?

The U.S. Supreme Court took up the question of whether courts must find a juvenile offender permanently incorrigible before a sentence of life without parole.

This Quality Counts 2019 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes.

Public schools in West Virginia are closed despite a deal that was supposed to end the teacher strike today.

Michael Martirano led the state's schools through dramatic budget cuts, academic challenges, and a state-versus-local battle over school construction.

In Tuesday night's Republican primary in West Virginia, Robert Karnes, a West Virginia Republican state senator who lashed out at teachers during their nine-day strike, lost to pro-labor candidate Bill Hamilton.

The legislature sent a proposal last week to Gov. Jim Justice's desk to shutter the state's advisory education and the arts department, leaving the Gayle Manchin and her staff in the lurch.

Teachers will receive a 5 percent raise, pending a vote by the state legislature. School will resume Thursday.

The West Virginia Senate trimmed the proposed pay raise for teachers from 5 percent to 4 percent, prompting union officials to declare that the strike will continue indefinitely.

The statewide teacher strike could end today if both chambers of the legislature pass the bill to deliver a 5 percent raise to all school employees.

The West Virginia House of Delegates passed its version of a sweeping education omnibus bill, which would allow the state's first charter schools.

Lawmakers effectively killed the controversial education bill that had prompted the second statewide strike in two years.

Teachers across the state will walk out of their classrooms on Tuesday to protest an education bill going through the state legislature.

This Quality Counts 2020 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes.

After a couple years of clashes with teachers in the state, West Virginia Senate President Mitch Carmichael was ousted in Tuesday's Republican primary election by a teacher.

Districts are reconfiguring services, offering hazard pay, and partnering with food banks to keep up with a growing, unprecedented demand for food services during the school shutdown.

Lawmakers in Illinois are considering a bill that would require children to start kindergarten if they are 5 on or before May 31, with exceptions for summer birthdays.

The state's decision indicates that U.S. Secretary of Education Betsy DeVos' push on COVID-19 and private school students is having an affect.

While the Lady Vols volunteered at the Girls Inc. basketball clinic, they reminded Nicky Anosike of her own Tennessee teammates

UConn women’s basketball freshman Sarah Strong earned the first Big East Freshman of the Week honors of her career on Monday after a pair of impressive performances in the Huskies’ Week 1 wins. Strong was the No. 1 recruit in the Class of 2024 and lived up to her elite billing with a game-high 17 points in her college debut against Boston University on Thursday. She also led the team with six ...

Three stars from Iowa women's basketball's 71-52 victory vs. Virginia Tech.

Nov. 11—Class 3A preseason No. 1 Greensburg opened the season Friday with an 81-23 victory over Jac-Cen-Del. The Lady Pirates opened the scoring with a steal and layup by Mylie Wilkison. After buckets by Clarie Larrison, Mary Harmon, Wilkison and Leah West, the Lady Pirates led 10-0. JCD got on the board with a 3-pointer by Brooklyn Simon. It was all Greensburg from there in the first quarter. ...

Tennessee soccer earned an NCAA Tournament berth for the fourth straight season and will face No. 7 seed Virginia Tech in the first round Friday

EAU CLAIRE— This weekend saw the first basketball games for Blugold men’s and women’s basketball during the Market & Johnson Blugold Tip-Off Tournament. The games were the first to be played at the Sonnentag Event Center, a part of the new $122 million multi-purpose facility which opened earlier this year. The event center has a capacity of 3,500 people for sporting events as compared to the ...

Wen Grace Chen
Nov 9, 2022; 42:8498-8507
Symposium and Mini-Symposium

Rafael G. Almeida
Oct 18, 2017; 37:10023-10034
Viewpoints

Mahsa Altafi
Oct 23, 2024; 44:e0518242024-e0518242024
Systems/Circuits

Elena Neumann
Oct 9, 2024; 44:e0591242024-e0591242024
Systems/Circuits

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

AP Georgopoulos
Nov 1, 1982; 2:1527-1537
Articles

John M. Beggs
Dec 3, 2003; 23:11167-11177
BehavioralSystemsCognitive

Targeting altered expression and/or activity of GABA (-aminobutyric acid) transporters (GATs) provide therapeutic benefit for age-related impairments, including cognitive dysfunction. However, the mechanisms underlying the transcriptional regulation of GATs are unknown. In the present study, we demonstrated that the stimulator of interferon genes (STING) upregulates GAT1 and GAT3 expression in the brain, which resulted in cognitive dysfunction. Genetic and pharmacological intervention of STING suppressed the expression of both GAT1 and GAT3, increased the ambient GABA concentration, and therefore, enhanced tonic GABA_A inhibition of principal hippocampal neurons, resulting in spatial learning and working memory deficits in mice in a type I interferon-independent manner. Stimulation of the STING->GAT pathway efficiently restored cognitive dysfunction in STING-deficient mice models. Our study uncovered for the first time that the STING signaling pathway regulates GAT expression in a cell autonomous manner and therefore could be a novel target for GABAergic cognitive deficits.

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.

GABAergic neurons and GABA_A receptors (GABA_ARs) are critical elements of almost all neuronal circuits. Most GABA_ARs of the CNS are heteropentameric ion channels composed of two α, two β, and one subunits. These receptors serve as important drug targets for benzodiazepine (BDZ) site agonists, which potentiate the action of GABA at GABA_ARs. Most GABA_AR classifications rely on the heterogeneity of the α subunit (α1–α6) included in the receptor complex. Heterogeneity of the subunits (1–3), which mediate synaptic clustering of GABA_ARs and contribute, together with α subunits, to the benzodiazepine (BDZ) binding site, has gained less attention, mainly because 2 subunits greatly outnumber the other subunits in most brain regions. Here, we have investigated a potential role of non-2 GABA_ARs in neural circuits of the spinal dorsal horn, a key site of nociceptive processing. Female and male mice were studied. We demonstrate that besides 2 subunits, 1 subunits are significantly expressed in the spinal dorsal horn, especially in its superficial layers. Unlike global 2 subunit deletion, which is lethal, spinal cord-specific loss of 2 subunits was well tolerated. GABA_AR clustering in the superficial dorsal horn remained largely unaffected and antihyperalgesic actions of HZ-166, a nonsedative BDZ site agonist, were partially retained. Our results thus suggest that the superficial dorsal horn harbors functionally relevant amounts of 1 subunits that support the synaptic clustering of GABA_ARs in this site. They further suggest that 1 containing GABA_ARs contribute to the spinal control of nociceptive information flow.

Vertebrate nervous systems use the axon initial segment (AIS) to initiate action potentials and maintain neuronal polarity. The microtubule-associated protein tripartite motif containing 46 (TRIM46) was reported to regulate axon specification, AIS assembly, and neuronal polarity through the bundling, or fasciculation, of microtubules in the proximal axon. However, these claims are based on TRIM46 knockdown in cultured neurons. To investigate TRIM46 function in vivo, we examined male and female TRIM46 knock-out mice. Contrary to previous reports, we find that TRIM46 is dispensable for axon specification and AIS formation. TRIM46 knock-out mice are viable, have normal behavior, and have normal brain structure. Thus, TRIM46 is not required for AIS formation, axon specification, or nervous system function. However, we confirm that TRIM46 is required for microtubule fasciculation. We also show TRIM46 enrichment in the first ~100 μm of axon occurs independently of ankyrinG (AnkG) in vivo, although AnkG is required to restrict TRIM46 only to the AIS. Our results highlight the need for further investigation of the mechanisms by which the AIS and microtubules interact to shape neuronal structure and function.

Cochlear hair cells (HCs) sense sound waves and allow us to hear. Loss of HCs will cause irreversible sensorineural hearing loss. It is well known that DNA damage repair plays a critical role in protecting cells in many organs. However, how HCs respond to DNA damage and how defective DNA damage repair contributes to hearing loss remain elusive. In this study, we showed that cisplatin induced DNA damage in outer hair cells (OHCs) and promoted OHC loss, leading to hearing loss in mice of either sex. Cisplatin induced the expression of Brca1, a DNA damage repair factor, in OHCs. Deficiency of Brca1 induced OHC and hearing loss, and further promoted cisplatin-induced DNA damage in OHCs, accelerating OHC loss. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in OHCs and that BRCA1 promotes repair of DNA damage in OHCs and prevents hearing loss. Our findings not only demonstrate that DNA damage–inducing agent generates DNA damage in postmitotic HCs but also suggest that DNA repair factors, like BRCA1, protect postmitotic HCs from DNA damage–induced cell death and hearing loss.

Neural circuits supporting innate behaviors, such as feeding, exploration, and social interaction, intermingle in the lateral hypothalamus (LH). Although previous studies have shown that individual LH neurons change their firing relative to the baseline during one or more behaviors, the firing rate dynamics of LH populations within behavioral episodes and the coordination of behavior-related LH populations remain largely unknown. Here, using unsupervised graph-based clustering of LH neurons firing rate dynamics in freely behaving male mice, we identified distinct populations of cells whose activity corresponds to feeding, specific times during feeding bouts, or other innate behaviors—social interaction and novel object exploration. Feeding-related cells fired together with a higher probability during slow and fast gamma oscillations (30–60 and 60–90 Hz) than during nonrhythmic epochs. In contrast, the cofiring of neurons signaling other behaviors than feeding was overall similar between slow gamma and nonrhythmic epochs but increased during fast gamma oscillations. These results reveal a neural organization of ethological hierarchies in the LH and point to behavior-specific motivational systems, the dysfunction of which may contribute to mental disorders.

Neuroinflammation can positively influence axon regeneration following injury in the central nervous system. Inflammation promotes the release of neurotrophic molecules and stimulates intrinsic proregenerative molecular machinery in neurons, but the detailed mechanisms driving this effect are not fully understood. We evaluated how microRNAs are regulated in retinal neurons in response to intraocular inflammation to identify their potential role in axon regeneration. We found that miR-383-5p is downregulated in retinal ganglion cells in response to zymosan-induced intraocular inflammation. MiR-383-5p downregulation in neurons is sufficient to promote axon growth in vitro, and the intravitreal injection of a miR-383-5p inhibitor into the eye promotes axon regeneration following optic nerve crush. MiR-383-5p directly targets ciliary neurotrophic factor (CNTF) receptor components, and miR-383-5p inhibition sensitizes adult retinal neurons to the outgrowth-promoting effects of CNTF. Interestingly, we also demonstrate that CNTF treatment is sufficient to reduce miR-383-5p levels in neurons, constituting a positive-feedback module, whereby initial CNTF treatment reduces miR-383-5p levels, which then disinhibits CNTF receptor components to sensitize neurons to the ligand. Additionally, miR-383-5p inhibition derepresses the mitochondrial antioxidant protein peroxiredoxin-3 (PRDX3) which was required for the proregenerative effects associated with miR-383-5p loss-of-function in vitro. We have thus identified a positive-feedback mechanism that facilitates neuronal CNTF sensitivity in neurons and a new molecular signaling module that promotes inflammation-induced axon regeneration.

The capabilities of the human ear are remarkable. We can normally detect acoustic stimuli down to a threshold sound-pressure level of 0 dB (decibels) at the entrance to the external ear, which elicits eardrum vibrations in the picometer range. From this threshold up to the onset of pain, 120 dB, our ears can encompass sounds that differ in power by a trillionfold. The comprehension of speech and enjoyment of music result from our ability to distinguish between tones that differ in frequency by only 0.2%. All these capabilities vanish upon damage to the ear's receptors, the mechanoreceptive sensory hair cells. Each cochlea, the auditory organ of the inner ear, contains some 16,000 such cells that are frequency-tuned between ~20 Hz (cycles per second) and 20,000 Hz. Remarkably enough, hair cells do not simply capture sound energy: they can also exhibit an active process whereby sound signals are amplified, tuned, and scaled. This article describes the active process in detail and offers evidence that its striking features emerge from the operation of hair cells on the brink of an oscillatory instability—one example of the critical phenomena that are widespread in physics.

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.