Enhancing arthropod occurrence in wheat cropping systems: the role of non-chemical pest management and nitrogen optimization.

This study analyzes arthropod biomass and abundance to track the changes in arthropod occurrence in relation to pesticide use in three winter wheat cropping systems managed at different intensities (organic, conventional, and hybrid). Arthropod occurrence was surveyed using three collection tools: sweeping nets, eclector traps, and yellow traps. Sampling was conducted over three years from 2020 to 2022 with 588 samples collected. The wet weight of the captured organisms was determined and arthropod abundance calculated. The application of a NOcsPS (no chemical-synthetic pesticides) strategy, a new hybrid cultivation method realized with optimized use of nitrogen fertilizers but without chemical-synthetic pesticides, showed a higher arthropod occurrence and performed more convincingly regarding produced arthropod biomass and abundance than the other cropping variants. The results also demonstrate a dependence of the obtained insect indices on the collection method. Although arthropod biomass and abundance correlated for all collection methods, the combination of various methods as well as multiple procedures of sample analysis gives a more realistic and comprehensive view of the impact of the wheat cultivation systems on the arthropod fauna than one-factor analyses.

Functional Inhibition of Katanin Affects Synaptic Plasticity.

Dynamic microtubules critically regulate synaptic functions, but the role of microtubule severing in these processes is barely understood. Katanin is a neuronally expressed microtubule-severing complex regulating microtubule number and length in cell division or neurogenesis; however, its potential role in synaptic functions has remained unknown. Studying mice from both sexes, we found that katanin is abundant in neuronal dendrites and can be detected at individual excitatory spine synapses. Overexpression of a dominant-negative ATPase-deficient katanin subunit to functionally inhibit severing alters the growth of microtubules in dendrites, specifically at premature but not mature neuronal stages without affecting spine density. Notably, interference with katanin function prevented structural spine remodeling following single synapse glutamate uncaging and significantly affected the potentiation of AMPA-receptor-mediated excitatory currents after chemical induction of long-term potentiation. Furthermore, katanin inhibition reduced the invasion of microtubules into fully developed spines. Our data demonstrate that katanin-mediated microtubule severing regulates structural and functional plasticity at synaptic sites.

Prevalence and Abundance of Bacterial Pathogens of Concern in Shrimp, Catfish and Tilapia Obtained at Retail Stores in Maryland, USA.

Outbreaks of human gastroenteritis have been linked to the consumption of contaminated domestic and imported seafood. This study investigated the microbiological quality of seafood obtained from retail stores on the Eastern Shore of Maryland. A total of 440 samples of domestic and imported frozen shrimp, catfish and tilapia samples were analyzed for aerobic plate count (APC), total coliforms, Escherichia coli and seafood-borne-pathogens (Vibrio parahaemolyticus, Vibrio vulnificus, Salmonella, Campylobacter jejuni). The prevalence of APC, coliforms and E. coli positive samples was 100%, 43% and 9.3%, respectively. Approximately 3.2%, 1.4%, 28.9% and 3.6% of the samples were positive for V. parahaemolyticus, V. vulnificus, Salmonella and Campylobacter jejuni, respectively. The MPN/g ranges were 150-1100 MPN/g for vibrios, 10-1100 MPN/g for Salmonella and 93-460 MPN/g for C. jejuni in seafood, respectively. Comparing bacterial prevalence by type or source of seafood, the only significant difference identified was Salmonella-positive imported tilapia (33.3%) versus domestic tilapia (19.4%). The quantitative data on pathogen levels in the present study provide additional information for quantitative risk assessment not available in previous surveys. The findings of this study suggest the association of potential food safety hazards with domestic and imported seafood and warrant further large-scale studies and risk assessment.

Mechanism of external K+ sensitivity of KCNQ1 channels.

KCNQ1 voltage-gated K+ channels are involved in a wide variety of fundamental physiological processes and exhibit the unique feature of being markedly inhibited by external K+. Despite the potential role of this regulatory mechanism in distinct physiological and pathological processes, its exact underpinnings are not well understood. In this study, using extensive mutagenesis, molecular dynamics simulations, and single-channel recordings, we delineate the molecular mechanism of KCNQ1 modulation by external K+. First, we demonstrate the involvement of the selectivity filter in the external K+ sensitivity of the channel. Then, we show that external K+ binds to the vacant outermost ion coordination site of the selectivity filter inducing a diminution in the unitary conductance of the channel. The larger reduction in the unitary conductance compared to whole-cell currents suggests an additional modulatory effect of external K+ on the channel. Further, we show that the external K+ sensitivity of the heteromeric KCNQ1/KCNE complexes depends on the type of associated KCNE subunits.

Prevalence and antibiotic resistance of Salmonella in organic and non-organic chickens on the Eastern Shore of Maryland, USA.

Introduction: Salmonella infections have been intensely increasing and becoming a universal public health crisis. This study investigated the prevalence of Salmonella in organic and non-organic chickens and the antimicrobial resistance profiles and virulence genes (invA, pagC, and spvC) in recovered Salmonella isolates. Methods: Whole chicken carcasses [organic (n = 240) and non-organic (n = 240)] were obtained monthly for 1 year (n = 480) from a retail store on the Eastern Shore of Maryland. Salmonella isolation and identification were conducted by following the whole carcass enrichment method recommended by USDA-FSIS. Confirmed Salmonella isolates (organic n = 76; non-organic n = 137) were serotyped and tested for antibiotic susceptibility and virulence genes using standard methods. Results: Forty-nine percent (237/480) of the carcasses were positive for Salmonella. Organic and non-organic positivity rates were 37.1 and 61.8%, respectively. A significantly higher Salmonella contamination was observed in non-organic chickens (p < 0.05). The most common serovars were Salmonella Kentucky (47%), S. Infantis (35%), S. Enteritidis (6%), S. Typhimurium (5%), and S. Blockley (4%). Isolates were frequently resistant to at least one antibiotic (91.24%) or multidrug resistant (45.54%). Resistance was observed to tetracycline (82.8%), minocycline (42.3%), nitrofurantoin (40.3%), cefazolin (38.3%), ampicillin (32.1%), and ceftriaxone (26%). All isolates were susceptible to fluoroquinolone, carbapenem, and glycylcycline. The majority of isolates (99.1%) possessed at least one of three virulence genes of concern and 4.2% tested positive for all three. Ninety-five, 89, and 6.6% of isolates contained invA, pagC, and spvC genes, respectively. The spvC gene was not detected in serovars recovered from organic chickens though 92% and 82% of isolates were positive for invA and pagC. The frequency of Salmonella recovered from non-organic chickens possessing invA, pagC, and spvC genes were 97.1, 89.8, and 10.2%, respectively. Detection of invA and pagC genes showed no significant difference (p > 0.05) between organic and non-organic chickens but a significantly higher spvC gene (p < 0.05) was detected in non-organic chickens due to the majority of S. Enteritidis (92.3%) exclusively recovered from non-organic chicken carried spvC gene. Discussion: This study reveals a high prevalence of Salmonella in both organic and non-organic chickens, which exhibit resistance to vital antibiotics and carry virulence genes, thereby creating a potential risk of salmonellosis.

Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes.

Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine Mkln1 knockout causes non-habituating locomotor activity, increased exploratory drive, and decreased locomotor response to amphetamine. Muskelin deficiency impairs social novelty detection while promoting the retention of spatial reference memory and fear extinction recall. This is strongly mirrored in either weaker or stronger resting-state functional connectivity between critical circuits mediating locomotor exploration and cognition. We show that Mkln1 deletion alters dendrite branching and spine structure, coinciding with enhanced AMPAR-mediated synaptic transmission but selective impairment in synaptic potentiation maintenance. We identify muskelin at excitatory synapses and highlight its role in regulating dendritic spine actin stability. Our findings point to aberrant spine actin modulation and changes in glutamatergic synaptic function as critical mechanisms that contribute to the neurobehavioral phenotype arising from Mkln1 ablation.

Efficacy and Quality Attributes of Antimicrobial Agent Application via a Commercial Electrostatic Spray Cabinet To Inactivate Salmonella on Chicken Thigh Meat.

ABSTRACT: Salmonella is a foodborne pathogen associated with poultry meat. This study aimed to determine the efficiency and quality attributes of two antimicrobial agents to reduce Salmonella on raw chicken meat when applied individually and in combination using an electrostatic spray cabinet. Thus, 5 log CFU/g of nonpathogenic, rifampin-resistant Salmonella Typhimurium was inoculated on skinless, boneless, raw chicken thigh meat and passed through an electrostatic spray cabinet while being sprayed with 5% lauric arginate (LAE), and 100, 1,000, 1,500, and 1,750 ppm of peracetic acid (PAA). Spraying of 5% LAE for 45 s significantly reduced Salmonella by 5 log (P < 0.05). The 1,500 ppm of PAA reduced Salmonella significantly within 45 s (1.157 log). Spraying of 1,500 ppm of PAA followed by LAE within 15 s reduced Salmonella significantly more than vice versa (P < 0.05). The color, water holding capacity, and texture did not differ significantly but resulted in significantly strong aroma and flavor. Both LAE and PAA efficiently reduced Salmonella when applied in an electrostatic spray cabinet on raw chicken thigh meat. The results suggest that the sequential order of application of antimicrobial agents is important to improve the safety and quality of raw chicken thigh meat.

Function of K2P channels in the mammalian node of Ranvier.

In myelinated nerve fibres, action potentials are generated at nodes of Ranvier. These structures are located at interruptions of the myelin sheath, forming narrow gaps with small rings of axolemma freely exposed to the extracellular space. The mammalian node contains a high density of Na+ channels and K+ -selective leakage channels. Voltage-dependent Kv1 channels are only present in the juxta-paranode. Recently, the leakage channels have been identified as K2P channels (TRAAK, TREK-1). K2P channels are K+ -selective 'background' channels, characterized by outward rectification and their ability to be activated, e.g. by temperature, mechanical stretch or arachidonic acid. We are only beginning to elucidate the peculiar functions of nodal K2P channels. I will discuss two functions of the nodal K2P-mediated conductance. First, at body temperature K2P channels have a high open probability, thereby inducing a resting potential of about -85 mV. This negative resting potential reduces steady-state Na+ channel inactivation and ensures a large Na+ inward current upon a depolarizing stimulus. Second, the K2P conductance is involved in nodal action potential repolarization. The identification of nodal K2P channels is exciting since it shows that the nodal K+ conductance is not a fixed value but can be changed: it can be increased or decreased by a broad range of K2P modulators, thereby modulating, for example, the resting potential. The functional importance of nodal K2P channels will be exemplified by describing in more detail the function of the K2P conductance increase by raising the temperature from room temperature to 37°C.

Effect of lignin-blocking agent on enzyme hydrolysis of acid pretreated hemp waste.

Hemp wastes (stems and branches), fractionated after hemp flower extraction for the production of cannabidiol oil, were utilized as a potentially renewable resource for the sugar flatform process. Hydrolysis of cellulose from the acid pretreated hemp biomass using a commercial enzyme was tested and evaluated for its chemical composition, morphological change, and sugar recovery. Acid pretreated hemp stems and branches, containing 1% glucan (w/v) solids, were hydrolyzed for 72 h using 25 mg enzyme protein per g glucan. A 54% glucose conversion was achieved from the treated branches versus a 71% yield from the treated stems. Raw branches and stems yielded 35% and 38% glucose, respectively. Further tests with a lignin-blocking additive (e.g. bovine serum albumin) resulted in a 72% glucose yield increase for stem hydrolysis using 10 mg enzyme protein per g glucan. While pretreatment promotes amorphous hemicellulose decrease and cellulose decomposition, it causes enzyme inhibition/deactivation due to potential inhibitors (phenols and lignin-derived compounds). This study confirms the addition of non-catalytic proteins enhances the cellulose conversion by avoiding non-productive binding of enzymes to the lignin and lignin-derived molecules, with lignin content determining the degree of inhibition and conversion efficiency.

Recovery Rate of Cells of the Seven Regulated Serogroups of Shiga Toxin-Producing Escherichia coli from Raw Veal Cutlets, Ground Veal, and Ground Beef from Retail Stores in the Mid-Atlantic Region of the United States.

ABSTRACT: A total of 482 veal cutlet, 555 ground veal, and 540 ground beef samples were purchased from retail establishments in the mid-Atlantic region of the United States over a noncontiguous 2-year period between 2014 and 2017. Samples (325 g each) were individually enriched and screened via real-time PCR for all seven regulated serogroups of Shiga toxin-producing Escherichia coli (STEC). Presumptive STEC-positive samples were subjected to serogroup-specific immunomagnetic separation and plated onto selective media. Up to five isolates typical for STEC from each sample were analyzed via multiplex PCR for both the virulence genes (i.e., eae, stx1 and/or stx2, and ehxA) and serogroup-specific gene(s) for the seven regulated STEC serogroups. The recovery rates of non-O157 STEC from veal cutlets (3.94%, 19 of 482 samples) and ground veal (7.03%, 39 of 555 samples) were significantly higher (P < 0.05) than that from ground beef (0.93%, 5 of 540 samples). In contrast, only a single isolate of STEC O157:H7 was recovered; this isolate originated from 1 (0.18%) of 555 samples of ground veal. Recovery rates for STEC were not associated with state, season, packaging type, or store type (P > 0.05) but were associated with brand and fat content (P < 0.05). Pulsed-field subtyping of the 270 viable and confirmed STEC isolates from the 64 total samples testing positive revealed 78 pulsotypes (50 to 80% similarity) belonging to 39 pulsogroups, with ≥90% similarity among pulsotypes within pulsogroups. Multiple isolates from 43 (67.7%) of 64 samples testing positive had an indistinguishable pulsotype. STEC serotypes O26 and O103 were the most prevalent serogroups in beef and veal, respectively. These findings support related findings from regulatory sampling studies over the past decade and confirm that recovery rates for the regulated STEC serogroups are higher for raw veal than for raw beef samples, as was observed in the present study of meat purchased at food retailers in the mid-Atlantic region of the United States.

Spastin depletion increases tubulin polyglutamylation and impairs kinesin-mediated neuronal transport, leading to working and associative memory deficits.

Mutations in the gene encoding the microtubule-severing protein spastin (spastic paraplegia 4 [SPG4]) cause hereditary spastic paraplegia (HSP), associated with neurodegeneration, spasticity, and motor impairment. Complicated forms (complicated HSP [cHSP]) further include cognitive deficits and dementia; however, the etiology and dysfunctional mechanisms of cHSP have remained unknown. Here, we report specific working and associative memory deficits upon spastin depletion in mice. Loss of spastin-mediated severing leads to reduced synapse numbers, accompanied by lower miniature excitatory postsynaptic current (mEPSC) frequencies. At the subcellular level, mutant neurons are characterized by longer microtubules with increased tubulin polyglutamylation levels. Notably, these conditions reduce kinesin-microtubule binding, impair the processivity of kinesin family protein (KIF) 5, and reduce the delivery of presynaptic vesicles and postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Rescue experiments confirm the specificity of these results by showing that wild-type spastin, but not the severing-deficient and disease-associated K388R mutant, normalizes the effects at the synaptic, microtubule, and transport levels. In addition, short hairpin RNA (shRNA)-mediated reduction of tubulin polyglutamylation on spastin knockout background normalizes KIF5 transport deficits and attenuates the loss of excitatory synapses. Our data provide a mechanism that connects spastin dysfunction with the regulation of kinesin-mediated cargo transport, synapse integrity, and cognition.

The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier.

TRAAK is a membrane tension-activated K+ channel that has been associated through behavioral studies to mechanical nociception. We used specific monoclonal antibodies in mice to show that TRAAK is localized exclusively to nodes of Ranvier, the action potential propagating elements of myelinated nerve fibers. Approximately 80 percent of myelinated nerve fibers throughout the central and peripheral nervous system contain TRAAK in what is likely an all-nodes or no-nodes per axon fashion. TRAAK is not observed at the axon initial segment where action potentials are first generated. We used polyclonal antibodies, the TRAAK inhibitor RU2 and node clamp amplifiers to demonstrate the presence and functional properties of TRAAK in rat nerve fibers. TRAAK contributes to the 'leak' K+ current in mammalian nerve fiber conduction by hyperpolarizing the resting membrane potential, thereby increasing Na+ channel availability for action potential propagation. We speculate on why nodes of Ranvier contain a mechanosensitive K+ channel.

Myosin XVI Regulates Actin Cytoskeleton Dynamics in Dendritic Spines of Purkinje Cells and Affects Presynaptic Organization.

The actin cytoskeleton is crucial for function and morphology of neuronal synapses. Moreover, altered regulation of the neuronal actin cytoskeleton has been implicated in neuropsychiatric diseases such as autism spectrum disorder (ASD). Myosin XVI is a neuronally expressed unconventional myosin known to bind the WAVE regulatory complex (WRC), a regulator of filamentous actin (F-actin) polymerization. Notably, the gene encoding the myosin's heavy chain (MYO16) shows genetic association with neuropsychiatric disorders including ASD. Here, we investigated whether myosin XVI plays a role for actin cytoskeleton regulation in the dendritic spines of cerebellar Purkinje cells (PCs), a neuronal cell type crucial for motor learning, social cognition and vocalization. We provide evidence that both myosin XVI and the WRC component WAVE1 localize to PC spines. Fluorescence recovery after photobleaching (FRAP) analysis of GFP-actin in cultured PCs shows that Myo16 knockout as well as PC-specific Myo16 knockdown, lead to faster F-actin turnover in the dendritic spines of PCs. We also detect accelerated F-actin turnover upon interference with the WRC, and upon inhibition of Arp2/3 that drives formation of branched F-actin downstream of the WRC. In contrast, inhibition of formins that are responsible for polymerization of linear actin filaments does not cause faster F-actin turnover. Together, our data establish myosin XVI as a regulator of the postsynaptic actin cytoskeleton and suggest that it is an upstream activator of the WRC-Arp2/3 pathway in PC spines. Furthermore, ultra-structural and electrophysiological analyses of Myo16 knockout cerebellum reveals the presence of reduced numbers of synaptic vesicles at presynaptic terminals in the absence of the myosin. Therefore, we here define myosin XVI as an F-actin regulator important for presynaptic organization in the cerebellum.

Myosin VI Drives Clathrin-Mediated AMPA Receptor Endocytosis to Facilitate Cerebellar Long-Term Depression.

Myosin VI is an actin-based cytoskeletal motor implicated in various steps of membrane trafficking. Here, we investigated whether this myosin is crucial for synaptic function and plasticity in neurons. We find that myosin VI localizes at cerebellar parallel fiber to Purkinje cell synapses and that the myosin is indispensable for long-term depression of AMPA-receptor-mediated synaptic signal transmission at this synapse. Moreover, direct visualization of GluA2-containing AMPA receptors in Purkinje cells reveals that the myosin drives removal of AMPA receptors from the surface of dendritic spines in an activity-dependent manner. Co-immunoprecipitation and super-resolution microscopy indicate that specifically the interaction of myosin VI with the clathrin adaptor component α-adaptin is important during long-term depression. Together, these data suggest that myosin VI directly promotes clathrin-mediated endocytosis of AMPA receptors in Purkinje cells to mediate cerebellar long-term depression. Our results provide insights into myosin VI function and the molecular mechanisms underlying synaptic plasticity.

The Effect of Previous Life Cycle Phase on the Growth Kinetics, Morphology, and Antibiotic Resistance of Salmonella Typhimurium DT104 in Brain Heart Infusion and Ground Chicken Extract.

Growth models are predominately used in the food industry to estimate the potential growth of selected microorganisms under environmental conditions. The growth kinetics, cellular morphology, and antibiotic resistance were studied throughout the life cycle of Salmonella Typhimurium. The effect of the previous life cycle phase [late log phase (LLP), early stationary phase (ESP), late stationary phase (LSP), and early death phase (EDP)] of Salmonella after reinoculation in brain heart infusion broth (BHI), ground chicken extract (GCE), and BHI at pH 5, 7, and 9 and salt concentrations 2, 3, and 4% was investigated. The growth media and previous life cycle phase had significant effects on the lag time (λ), specific growth rate (µ max), and maximum population density (Y max). At 2 and 4% salt concentration, the LLP had the significantly (p < 0.05) fastest µ max (1.07 and 0.69 log CFU/ml/h, respectively). As the cells transitioned from the late log phase (LLP) to the early death phase (EDP), the λ significantly (p < 0.05) increased. At pH 5 and 9, the EDP had a significantly (p < 0.05) lower Y max than the LLP, ESP, and LSP. As the cells transitioned from a rod shape to a coccoid shape in the EDP, the cells were more susceptible to antibiotics. The cells regained their resistance as they transitioned back to a rod shape from the EDP to the log and stationary phase. Our results revealed that growth kinetics, cell's length, shape, and antibiotic resistance were significantly affected by the previous life cycle phase. The results of this study also demonstrate that the previous life cycle should be considered when developing growth models of foodborne pathogens to better ensure the safety of poultry and poultry products.

Ether-à-go-go K+ channels: effective modulators of neuronal excitability.

Mammalian ether-à-go-go (EAG) channels are voltage-gated K+ channels. They are encoded by the KCNH gene family and divided into three subfamilies, eag (Kv10), erg (eag-related gene; Kv11) and elk (eag-like; Kv12). All EAG channel subtypes are expressed in the brain where they effectively modulate neuronal excitability. This Topical Review describes the biophysical properties of each of the EAG channel subtypes, their function in neurons and the neurological diseases induced by EAG channel mutations. In contrast to the function of erg currents in the heart, where they contribute to repolarization of the cardiac action potential, erg currents in neurons are involved in the maintenance of the resting potential, setting of action potential threshold and frequency accommodation. They can even support high frequency firing by preventing a depolarization-induced Na+ channel block. EAG channels are modulated differentially, e.g. eag channels by intracellular Ca2+ , erg channels by extracellular K+ and GPCRs, and elk channels by changes in pH. So far, only currents mediated by erg channels have been recorded in neurons with the help of selective blockers. Neuronal eag and elk currents have not been isolated due to the lack of suitable channel blockers. However, findings in KO mice indicate a physiological role of eag1 currents in synaptic transmission and an involvement of elk2 currents in cognitive performance. Human eag1 and eag2 gain-of-function mutations underlie syndromes associated with epileptic seizures.

Reduction of Salmonella in ground chicken using a bacteriophage.

This study's goal was to ascertain the effectiveness of a commercially available Salmonella bacteriophage during ground chicken production focusing on: water source, different Salmonella serovars, and time. Salmonella-free boneless, skinless chicken meat was inoculated with 4.0 Log CFU/cm2 of either a cocktail of 3 Salmonella isolates derived from ground chicken (GC) or a cocktail of 3 Salmonella strains not isolated from ground chicken (non-GC). Bacteriophages were spread onto the chicken using sterile tap or filtered water for 30 min or 8 h. Salmonella was recovered using standard plating method. Greater Salmonella reduction was observed when the bacteriophage was diluted in sterile tap water than in sterile filtered water: 0.39 Log CFU/cm2 and 0.23 Log CFU/cm2 reduction after 30 min, respectively (P < 0.05). The non-GC isolates showed reductions of 0.71 Log CFU/cm2 and 0.90 Log CFU/cm2 after 30 min and 8 h, respectively (P < 0.05). The GC isolates were less sensitive to the bacteriophage: 0.39 Log CFU/cm2 and 0.67 Log CFU/cm2 reductions after 30 min and 8 h, respectively (P < 0.05). In conclusion, bacteriophage reduction was dependent on water used to dilute the bacteriophage, Salmonella's susceptibility to the bacteriophage, and treatment time.

The Kinesin KIF21B Regulates Microtubule Dynamics and Is Essential for Neuronal Morphology, Synapse Function, and Learning and Memory.

The kinesin KIF21B is implicated in several human neurological disorders, including delayed cognitive development, yet it remains unclear how KIF21B dysfunction may contribute to pathology. One limitation is that relatively little is known about KIF21B-mediated physiological functions. Here, we generated Kif21b knockout mice and used cellular assays to investigate the relevance of KIF21B in neuronal and in vivo function. We show that KIF21B is a processive motor protein and identify an additional role for KIF21B in regulating microtubule dynamics. In neurons lacking KIF21B, microtubules grow more slowly and persistently, leading to tighter packing in dendrites. KIF21B-deficient neurons exhibit decreased dendritic arbor complexity and reduced spine density, which correlate with deficits in synaptic transmission. Consistent with these observations, Kif21b-null mice exhibit behavioral changes involving learning and memory deficits. Our study provides insight into the cellular function of KIF21B and the basis for cognitive decline resulting from KIF21B dysregulation.

Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory.

Neurotransmitter receptor density is a major variable in regulating synaptic strength. Receptors rapidly exchange between synapses and intracellular storage pools through endocytic recycling. In addition, lateral diffusion and confinement exchanges surface membrane receptors between synaptic and extrasynaptic sites. However, the signals that regulate this transition are currently unknown. GABAA receptors containing α5-subunits (GABAAR-α5) concentrate extrasynaptically through radixin (Rdx)-mediated anchorage at the actin cytoskeleton. Here we report a novel mechanism that regulates adjustable plasma membrane receptor pools in the control of synaptic receptor density. RhoA/ROCK signalling regulates an activity-dependent Rdx phosphorylation switch that uncouples GABAAR-α5 from its extrasynaptic anchor, thereby enriching synaptic receptor numbers. Thus, the unphosphorylated form of Rdx alters mIPSCs. Rdx gene knockout impairs reversal learning and short-term memory, and Rdx phosphorylation in wild-type mice exhibits experience-dependent changes when exposed to novel environments. Our data suggest an additional mode of synaptic plasticity, in which extrasynaptic receptor reservoirs supply synaptic GABAARs.