Nisin Inhibition of Gram-Negative Bacteria.

Aims: This study investigates the activity of the broad-spectrum bacteriocin nisin against a large panel of Gram-negative bacterial isolates, including relevant plant, animal, and human pathogens. The aim is to generate supportive evidence towards the use/inclusion of bacteriocin-based therapeutics and open avenues for their continued development. Methods and Results: Nisin inhibitory activity was screened against a panel of 575 strains of Gram-negative bacteria, encompassing 17 genera. Nisin inhibition was observed in 309 out of 575 strains, challenging the prevailing belief that nisin lacks effectiveness against Gram-negative bacteria. The genera Acinetobacter, Helicobacter, Erwinia, and Xanthomonas exhibited particularly high nisin sensitivity. Conclusions: The findings of this study highlight the promising potential of nisin as a therapeutic agent for several key Gram-negative plant, animal, and human pathogens. These results challenge the prevailing notion that nisin is less effective or ineffective against Gram-negative pathogens when compared to Gram-positive pathogens and support future pursuits of nisin as a complementary therapy to existing antibiotics. Significance and Impact of Study: This research supports further exploration of nisin as a promising therapeutic agent for numerous human, animal, and plant health applications, offering a complementary tool for infection control in the face of multidrug-resistant bacteria.

Including Pregnant and Lactating Women in Clinical Research: Moving Beyond Legal Liability.

This Viewpoint summarizes a new report from the National Academies of Sciences, Engineering, and Medicine that encourages the inclusion of pregnant and lactating individuals in clinical research.

Alterations in synapses and mitochondria induced by acute or chronic intermittent hypoxia in the pre-Bötzinger complex of rats: an ultrastructural triple-labeling study with immunocytochemistry and histochemistry.

Introduction: The pre-Bötzinger complex (pre-BötC), a kernel of inspiratory rhythmogenesis, is a heterogeneous network with excitatory glutamatergic and inhibitory GABAergic and glycinergic neurons. Inspiratory rhythm generation relies on synchronous activation of glutamatergic neuron, whilst inhibitory neurons play a critical role in shaping the breathing pattern, endowing the rhythm with flexibility in adapting to environmental, metabolic, and behavioral needs. Here we report ultrastructural alterations in excitatory, asymmetric synapses (AS) and inhibitory, symmetric synapses (SS), especially perforated synapses with discontinuous postsynaptic densities (PSDs) in the pre-BötC in rats exposed to daily acute intermittent hypoxia (dAIH) or chronic (C) IH. Methods: We utilized for the first time a combination of somatostatin (SST) and neurokinin 1 receptor (NK1R) double immunocytochemistry with cytochrome oxidase histochemistry, to reveal synaptic characteristics and mitochondrial dynamic in the pre-BötC. Results: We found perforated synapses with synaptic vesicles accumulated in distinct pools in apposition to each discrete PSD segments. dAIH induced significant increases in the PSD size of macular AS, and the proportion of perforated synapses. AS were predominant in the dAIH group, whereas SS were in a high proportion in the CIH group. dAIH significantly increased SST and NK1R expressions, whereas CIH led to a decrease. Desmosome-like contacts (DLC) were characterized for the first time in the pre-BötC. They were distributed alongside of synapses, especially SS. Mitochondria appeared in more proximity to DLC than synapses, suggestive of a higher energy demand of the DLC. Findings of single spines with dual AS and SS innervation provide morphological evidence of excitation-inhibition interplay within a single spine in the pre-BötC. In particular, we characterized spine-shaft microdomains of concentrated synapses coupled with mitochondrial positioning that could serve as a structural basis for synchrony of spine-shaft communication. Mitochondria were found within spines and ultrastructural features of mitochondrial fusion and fission were depicted for the first time in the pre-BötC. Conclusion: We provide ultrastructural evidence of excitation-inhibition synapses in shafts and spines, and DLC in association with synapses that coincide with mitochondrial dynamic in their contribution to respiratory plasticity in the pre-BötC.

Comparing Self-Management Programs with and without Peer Support among Patients with Chronic Obstructive Pulmonary Disease: A Clinical Trial.

Rationale: Self-management support (SMS) is an essential component of care for patients who have chronic obstructive pulmonary disease (COPD), but there is little evidence on how to provide SMS most effectively to these patients. Peer support (i.e., support provided by a person with a similar medical condition) has been successfully used to promote self-management among patients with various chronic conditions, yet no randomized studies have focused on testing its effects for patients with COPD. Objectives: To assess whether adding peer support to healthcare professional (HCP) support to help patients with COPD self-management results in better health-related quality of life (HRQoL) and less acute care use. Methods: A two-arm randomized controlled trial was performed at one academic and one community hospital and their affiliate clinics. The study population included patients aged ⩾40 years who had been diagnosed with COPD by a physician and were currently receiving daily treatment for it. Two self-management support strategies were compared over 6 months. One strategy relied on the HCP for COPD self-management (HCP support); the other used a dual approach involving both HCPs and peer supporters (HCP Plus Peer). The primary outcome was change in HRQoL measured by the St. George's Respiratory Questionnaire at 6 months (range, 0-100, lower is better; four-point meaningful difference). Secondary outcomes included COPD-related and all-cause hospitalizations and emergency department visits. Analysis was conducted under intention to treat. Results: The number of enrolled participants was 292. Mean age was 67.7 (standard deviation, 9.4) years; 70.9% of participants were White, and 61.3% were female. St. George's Respiratory Questionnaire scores were not significantly different between the study arms at 6 months. HCP Plus Peer arm participants had fewer COPD-related acute care events at 3 months (incidence rate ratio, 0.68; 95% confidence interval [CI], 0.50-0.93) and 6 months (incidence rate ratio, 0.84; 95% CI, 0.71-0.99). Conclusions: Adding peer support to HCP support to help patients self-manage COPD did not further improve HRQoL in this study. However, it did result in fewer COPD-related acute care events during the 6-month intervention period. Clinical trial registered with www.clinicaltrials.gov (NCT02891200).

Identifying more targeted antimicrobials active against selected bacterial phytopathogens.

AIMS: Phytopathogens are a global threat to the world's food supply. The use of broad-spectrum bactericides and antibiotics to limit or eliminate bacterial infections is becoming less effective as levels of resistance increase, while concurrently becoming less desirable from an ecological perspective due to their collateral damage to beneficial members of plant and soil microbiomes. Bacteria produce numerous antimicrobials in addition to antibiotics, such as bacteriocins with their relatively narrow activity spectra, and inhibitory metabolic by-products, such as organic acids. There is an interest in developing these naturally occurring antimicrobials for use as alternatives or supplements to antibiotics. METHODS AND RESULTS: In this study, we investigate the inhibitory potential of 217 plant-associated bacterial isolates from 44 species including plant pathogens, plant growth promoting rhizobacteria and plant commensals. Over half of the isolates were found to produce antimicrobial substances, of which 68% were active against phytopathogens. Even more intriguing, 98% of phytopathogenic strains were sensitive to the compounds produced specifically by plant growth promoting rhizobacteria. CONCLUSION: These data argue that plant-associated bacteria produce a broad range of antimicrobial substances, and that the substances produced preferentially target phytopathogenic bacteria. SIGNIFICANCE AND IMPACT OF STUDY: There is a need for novel antimicrobials for use in agriculture. The methods presented here reveal the potential for simple phenotypic screening methods to provide a broad range of potential drug candidates.

The critical period: neurochemical and synaptic mechanisms shared by the visual cortex and the brain stem respiratory system.

The landmark studies of Wiesel and Hubel in the 1960's initiated a surge of investigations into the critical period of visual cortical development, when abnormal visual experience can alter cortical structures and functions. Most studies focused on the visual cortex, with relatively little attention to subcortical structures. The goal of the present review is to elucidate neurochemical and synaptic mechanisms common to the critical periods of the visual cortex and the brain stem respiratory system in the normal rat. In both regions, the critical period is a time of (i) heightened inhibition; (ii) reduced expression of brain-derived neurotrophic factor (BDNF); and (iii) synaptic imbalance, with heightened inhibition and suppressed excitation. The last two mechanisms are contrary to the conventional premise. Synaptic imbalance renders developing neurons more vulnerable to external stressors. However, the critical period is necessary to enable each system to strengthen its circuitry, adapt to its environment, and transition from immaturity to maturity, when a state of relative synaptic balance is attained. Failure to achieve such a balance leads to neurological disorders.

Anion Exchange Doping: Tuning Equilibrium to Increase Doping Efficiency in Semiconducting Polymers.

High electron affinity (EA) molecules p-type dope low ionization energy (IE) polymers, resulting in an equilibrium doping level based on the energetic driving force (IE-EA), reorganization energy, and dopant concentration. Anion exchange doping (AED) is a process whereby the dopant anion is exchanged with a stable ion from an electrolyte. We show that the AED level can be predicted using an isotherm equilibrium model. The exchange of the dopant anion (FeCl3-) for a bis(trifluoromethanesulfonamide) (TFSI-) anion in the polymers poly(3-hexylthiophene-2,5-diyl) (P3HT) and poly[3-(2,2-bithien-5-yl)-2,5-bis(2-hexyldecyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione-6,5-diyl] (PDPP-2T) highlights two cases in which the process is nonspontaneous and spontaneous, respectively. For P3HT, FeCl3 provides a high doping level but an unstable counterion, so exchange results in an air stable counterion with a marginal increase in doping. For PDPP-2T, FeCl3 is a weak dopant, but the exchange of FeCl3- for TFSI- is spontaneous, so the doping level increases by >10× with AED.

Chronic intermittent hypoxia alters the dendritic mitochondrial structure and activity in the pre-Bötzinger complex of rats.

Mitochondrial bioenergetics is dynamically coupled with neuronal activities, which are altered by hypoxia-induced respiratory neuroplasticity. Here we report structural features of postsynaptic mitochondria in the pre-Bötzinger complex (pre-BötC) of rats treated with chronic intermittent hypoxia (CIH) simulating a severe condition of obstructive sleep apnea. The subcellular changes in dendritic mitochondria and histochemistry of cytochrome c oxidase (CO) activity were examined in pre-BötC neurons localized by immunoreactivity of neurokinin 1 receptors. Assays of mitochondrial electron transport chain (ETC) complex I, IV, V activities, and membrane potential were performed in the ventrolateral medulla containing the pre-BötC region. We found significant decreases in the mean length and area of dendritic mitochondria in the pre-BötC of CIH rats, when compared to the normoxic control and hypoxic group with daily acute intermittent hypoxia (dAIH) that evokes robust synaptic plasticity. Notably, these morphological alterations were mainly observed in the mitochondria in close proximity to the synapses. In addition, the proportion of mitochondria presented with enlarged compartments and filamentous cytoskeletal elements in the CIH group was less than the control and dAIH groups. Intriguingly, these distinct characteristics of structural adaptability were observed in the mitochondria within spatially restricted dendritic spines. Furthermore, the proportion of moderately to darkly CO-reactive mitochondria was reduced in the CIH group, indicating reduced mitochondrial activity. Consistently, mitochondrial ETC enzyme activities and membrane potential were lowered in the CIH group. These findings suggest that hypoxia-induced respiratory plasticity was characterized by spatially confined mitochondrial alterations within postsynaptic spines in the pre-BötC neurons. In contrast to the robust plasticity evoked by dAIH preconditioning, a severe CIH challenge may weaken the local mitochondrial bioenergetics that the fuel postsynaptic activities of the respiratory motor drive.

Should Networks Supplant Tree Building?

Recent studies suggested that network methods should supplant tree building as the basis of genealogical analysis. This proposition is based upon two arguments. First is the observation that bacterial and archaeal lineages experience processes oppositional to bifurcation and hence the representation of the evolutionary process in a tree like structure is illogical. Second is the argument tree building approaches are circular-you ask for a tree and you get one, which pins a verificationist label on tree building that, if correct, should be the end of phylogenetic analysis as we currently know it. In this review, we examine these questions and suggest that rumors of the death of the bacterial tree of life are exaggerated at best.

Results of a National Text Message Poll of Youth: Perspectives on Primary Care.

PURPOSE: There is a significant interest in improving adolescent access to primary care, yet limited attempts to incorporate youth feedback within these efforts. The purpose of this study was to describe the experiences related to primary care among a large national sample of adolescents to improve patient-centered care. METHODS: Youth were sent open-ended text message prompts via an ongoing study of 14- to 24-year-olds in the U.S. Text responses were analyzed using qualitative thematic analysis, including descriptive coding, consensus building, and theme development. Secondary quantitative analyses were conducted to determine differences by demographics. RESULTS: Of 1,123 eligible participants, 789 (70.2%) responded to at least one prompt. Four themes were developed: (1) youth recognized the importance of primary care, but barriers exist that limited their utilization; (2) youth felt that improving convenience would increase the use of primary care; (3) youth were unsure how to transition between primary care settings; and (4) feeling respected was essential to youth having positive experiences in a primary care health care setting. Older youth and those identifying as female, nonbinary, or transgender were more likely to report previous bad experiences with primary care. CONCLUSIONS: Our findings describe barriers and possible solutions to primary care among youth. Because attitudes toward health and health care are established during adolescence, a transformation is needed to create more patient-centered care that aligns with young people's values and experiences. Thus, primary care providers have the opportunity to positively impact the health of young people today and the adults of the future.

Health Maintenance in School-Aged Children: Part I. History, Physical Examination, Screening, and Immunizations.

The goals of the health maintenance visit in school-aged children (five to 12 years) are promoting health, detecting disease, and counseling to prevent injury and future health problems. During the visit, the physician should address patient and parent/caregiver concerns and ask about emergency department or hospital care since the last visit; lifestyle habits (diet, physical activity, daily screen time, secondhand smoke exposure, hours of sleep per night, dental care, safety habits); and school performance. Poor school performance may indicate problems such as learning disabilities, attention-deficit/hyperactivity disorder, or bullying. Previsit questionnaires and psychosocial screening questionnaires are also useful. When performing a physical examination, the physician should be alert for signs of abuse. Children should be screened for obesity (defined as body mass index at or above the 95th percentile for age and sex), and obese children should be referred for intensive behavioral interventions. Although its recommendations are primarily based on expert opinion, the American Academy of Pediatrics recommends screening for hypertension annually, vision and hearing problems approximately every two years, and dyslipidemia once between nine and 11 years of age; regular screening for risk factors related to social determinants of health is also recommended. There is insufficient evidence to recommend routine screening for depression before 12 years of age, but depression should be considered in children younger than 12 years presenting with unexplained somatic symptoms, restlessness, separation anxiety, phobias, or hallucinations. Children living in areas with inadequate levels of fluoride in the water supply (0.6 ppm or less) should receive daily fluoride supplements. Age-appropriate immunizations should be given, as well as any catch-up immunizations.

Evaluation of the potential of colicins to prevent extraluminal contamination of urinary catheters by Escherichia coli.

The feasibility of using colicins to create an antimicrobial lubricant to prevent extraluminal catheter contamination during urinary catheter insertion was assessed. Levels of resistance of uropathogenic Escherichia coli to antibiotics and colicins were compared. The results showed that antibiotics and colicins possess similar frequencies of resistance to a single drug, whereas colicins exhibit significantly lower levels of multidrug resistance (22%) than antibiotics (42%). Colicins and antibiotics showed complementary inhibitory activity, with each targeting different subsets of pathogenic isolates. The collateral impact of these two antimicrobials on genera that are members of the fecal/vaginal/urinary microbiome was assessed, with colicins showing significantly less collateral damage than antibiotics. Using a novel colicin, SR4, minimum inhibitory concentrations (MICs) for a panel of 30 uropathogenic isolates were determined and showed that SR4 achieved the same antimicrobial efficacy as gentamicin using 20-30% less drug. An SR4-impregnated catheter lubricant was created and its ability to prevent extraluminal urinary catheter contamination in vitro was demonstrated. These data indicate that a colicin-impregnated lubricant may provide a viable prophylactic option for preventing catheter-associated urinary tract infections.

Mechanisms underlying a critical period of respiratory development in the rat.

Twenty-five years ago, Filiano and Kinney (1994) proposed that a critical period of postnatal development constitutes one of the three risk factors for sudden infant death syndrome (SIDS). The underlying mechanism was poorly understood. In the last 17 years, much has been uncovered on this period in the rat. Against several expected trends of development, abrupt neurochemical, metabolic, ventilatory, and electrophysiological changes occur in the respiratory system at P12-13. This results in a transient synaptic imbalance with suppressed excitation and enhanced inhibition, and the response to acute hypoxia is the weakest at this time, both at the cellular and system's levels. The basis for the synaptic imbalance is likely to be contributed by a reduced expression of brain-derived neurotrophic factor (BDNF) and its TrkB receptors in multiple brain stem respiratory-related nuclei during the critical period. Exogenous BDNF or a TrkB agonist partially reverses the synaptic imbalance, whereas a TrkB antagonist accentuates the imbalance. A transient down-regulation of pituitary adenylate cyclase-activating polypeptide (PACAP) at P12 in respiratory-related nuclei also contributes to the vulnerability of this period. Carotid body denervation during this time or perinatal hyperoxia merely delays and sometimes prolongs, but not eliminate the critical period. The rationale for the necessity of the critical period in postnatal development is discussed.

Acute and chronic changes in the control of breathing in a rat model of bronchopulmonary dysplasia.

Infants born very prematurely (<28 wk gestation) have immature lungs and often require supplemental oxygen. However, long-term hyperoxia exposure can arrest lung development, leading to bronchopulmonary dysplasia (BPD), which increases acute and long-term respiratory morbidity and mortality. The neural mechanisms controlling breathing are highly plastic during development. Whether the ventilatory control system adapts to pulmonary disease associated with hyperoxia exposure in infancy remains unclear. Here, we assessed potential age-dependent adaptations in the control of breathing in an established rat model of BPD associated with hyperoxia. Hyperoxia exposure ( FIO2 ; 0.9 from 0 to 10 days of life) led to a BPD-like lung phenotype, including sustained reductions in alveolar surface area and counts, and modest increases in airway resistance. Hyperoxia exposure also led to chronic increases in room air and acute hypoxic minute ventilation (V̇e) and age-dependent changes in breath-to-breath variability. Hyperoxia-exposed rats had normal oxygen saturation ( SpO2 ) in room air but greater reductions in SpO2 during acute hypoxia (12% O2) that were likely due to lung injury. Moreover, acute ventilatory sensitivity was reduced at P12 to P14. Perinatal hyperoxia led to greater glial fibrillary acidic protein expression and an increase in neuron counts within six of eight or one of eight key brainstem regions, respectively, controlling breathing, suggesting astrocytic expansion. In conclusion, perinatal hyperoxia in rats induced a BPD-like phenotype and age-dependent adaptations in V̇e that may be mediated through changes to the neural architecture of the ventilatory control system. Our results suggest chronically altered ventilatory control in BPD.

Pituitary adenylate cyclase-activating polypeptide: Postnatal development in multiple brain stem respiratory-related nuclei in the rat.

The pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in anterior pituitary hormone secretion, neurotransmission, and the control of breathing. Mice lacking PACAP die suddenly mainly in the 2nd postnatal week, coinciding temporally with a critical period of respiratory development uncovered by our laboratory in the rat. The goal of the current study was to test our hypothesis that PACAP expression is reduced during the critical period in normal rats. We undertook immunohistochemistry and optical densitometry of PACAP (specifically PACAP38) in several brain stem respiratory-related nuclei of postnatal days P2-21 rats, and found that PACAP immunoreactivity was significantly reduced at P12 in the pre-Bötzinger complex, nucleus ambiguus, hypoglossal nucleus, and the ventrolateral subnucleus of the nucleus tractus solitarius. No changes were observed in the control, non-respiratory cuneate nucleus at P12. Results imply that the down-regulation of PACAP during normal postnatal development may contribute to the critical period of vulnerability, when the animals' response to hypoxia is at its weakest.

Daily acute intermittent hypoxia induced dynamic changes in dendritic mitochondrial ultrastructure and cytochrome oxidase activity in the pre-Bötzinger complex of rats.

Mitochondria, as primary energy generators and Ca2+ biosensor, are dynamically coupled to neuronal activities, and thus play a role in neuroplasticity. Here we report that respiratory neuroplasticity induced by daily acute intermittent hypoxia (dAIH) evoked adaptive changes in the ultrastructure and postsynaptic distribution of mitochondria in the pre-Bötzinger complex (pre-BötC). The metabolic marker of neuronal activity, cytochrome c oxidase (CO), and dendritic mitochondria were examined in pre-BötC neurons of adult Sprague-Dawley rats preconditioned with dAIH, which is known to induce long-term facilitation (LTF) in respiratory neural activities. We performed neurokinin 1 receptor (NK1R) pre-embedding immunocytochemistry to define pre-BötC neurons, in combination with CO histochemistry, to depict ultrastructural alterations and CO activity in dendritic mitochondria. We found that the dAIH challenge significantly increased CO activity in pre-BötC neurons. Darkly CO-reactive mitochondria at postsynaptic sites in the dAIH group were much more prevalent than those in the normoxic control. In addition, the length and area of mitochondria were significantly increased in the dAIH group, implying a larger surface area of cristae for ATP generation. There was a fine, structural remodeling, notably enlarged and branching mitochondria or tapered mitochondria extending into dendritic spines. Mitochondrial cristae were mainly in parallel-lamellar arrangement, indicating a high efficiency of energy generation. Moreover, flocculent or filament-like elements were noted between the mitochondria and the postsynaptic membrane. These morphological evidences, together with increased CO activity, demonstrate that dendritic mitochondria in the pre-BötC responded dynamically to respiratory plasticity. Hence, plastic neuronal changes are closely coupled to active mitochondrial bioenergetics, leading to enhanced energy production and Ca2+ buffering that may drive the LTF expression.

High Blood Pressure in Children and Adolescents.

High blood pressure in children and adolescents is a growing health problem that is often overlooked. Children should be screened for elevated blood pressure annually beginning at three years of age or at every visit if risk factors are present. In children younger than 13 years, elevated blood pressure is defined as blood pressure in the 90th percentile or higher for age, height, and sex, and hypertension is defined as blood pressure in the 95th percentile or higher. In adolescents 13 years and older, elevated blood pressure is defined as blood pressure of 120 to 129 mm Hg systolic and less than 80 mm Hg diastolic, and hypertension is defined as blood pressure of 130/80 mm Hg or higher. Ambulatory blood pressure monitoring should be performed to confirm hypertension in children and adolescents. Primary hypertension is now the most common cause of hypertension in children and adolescents. A history and physical examination and targeted screening tests should be done to evaluate for underlying medical disorders, and children and adolescents with hypertension should be screened for comorbid cardiovascular diseases, including diabetes mellitus and hyperlipidemia. Hypertension in children is initially treated with lifestyle changes such as weight loss if overweight or obese, a healthy diet, and regular exercise. Children with symptomatic hypertension (e.g., headaches, cognitive changes), stage 2 hypertension without a modifiable factor such as obesity, evidence of left ventricular hypertrophy on echocardiography, any stage of hypertension associated with chronic kidney disease or diabetes, or persistent hypertension despite a trial of lifestyle modifications require antihypertensive medications and should be evaluated for cardiovascular damage with echocardiography. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and thiazide diuretics are effective, safe, and well-tolerated in children.

Uncovering a critical period of synaptic imbalance during postnatal development of the rat visual cortex: role of brain-derived neurotrophic factor.

KEY POINTS: With daily electrophysiological recordings and neurochemical analysis, we uncovered a transient period of synaptic imbalance between enhanced inhibition and suppressed excitation in rat visual cortical neurons from the end of the fourth toward the end of the fifth postnatal weeks. The expression of brain-derived neurotrophic factor (BDNF), which normally enhances excitation and suppresses inhibition, was down-regulated during that time, suggesting that this may contribute to the inhibition/excitation imbalance. An agonist of the BDNF receptor tropomyosin-related kinase B (TrkB) partially reversed the imbalance, whereas a TrkB antagonist accentuated the imbalance during the transient period. Monocular lid suture during the transient period is more detrimental to the function and neurochemical properties of visual cortical neurons than before or after this period. We regard the period of synaptic imbalance as the peak critical period of vulnerability, and its existence is necessary for neurons to transition from immaturity to a more mature state of functioning. ABSTRACT: The mammalian visual cortex is immature at birth and undergoes postnatal structural and functional adjustments. The exact timing of the vulnerable period in rodents remains unclear. The critical period is characterized by inhibitory GABAergic maturation reportedly dependent on brain-derived neurotrophic factor (BDNF). However, most of the studies were performed on experimental/transgenic animals, questioning the relationship in normal animals. The present study aimed to conduct in-depth analyses of the synaptic and neurochemical development of visual cortical neurons in normal and monocularly-deprived rats and to determine specific changes, if any, during the critical period. We found that (i) against a gradual increase in excitation and inhibition with age, a transient period of synaptic and neurochemical imbalance existed with suppressed excitation and enhanced inhibition at postnatal days 28 to 33/34; (ii) during this window, the expression of BDNF and tropomyosin-related kinase B (TrkB) receptors decreased, along with glutamatergic GluN1 and GluA1 receptors and the metabolic marker cytochrome oxidase, whereas that of GABAA Rα1 receptors continued to rise; (iii) monocular deprivation reduced both excitatory and inhibitory synaptic activity and neurochemicals mainly during this period; and (iv) in vivo TrkB agonist partially reversed the synaptic imbalance in normal and monocularly-deprived neurons during this time, whereas a TrkB antagonist accentuated the imbalance. Thus, our findings highlight a transitory period of synaptic imbalance with a negative relationship between BDNF and inhibitory GABA. This brief critical period may be necessary in transitioning from an immature to a more mature state of visual cortical functioning.