Monoclonal antibodies in neuro-ophthalmology.

Neuro-ophthalmologic diseases include a broad range of disorders affecting the afferent and efferent visual pathways. Recently, monoclonal antibody (mAb) therapies have emerged as a promising targeted approach in the management of several of these complex conditions. Here, we describe the mechanism-specific applications and advancements in neuro-ophthalmologic mAb therapies. The application of mAbs in neuro-ophthalmologic diseases highlights our increasing understanding of disease-specific mechanisms in autoimmune conditions such as neuromyelitis optica, thyroid eye disease, and myasthenia gravis. Due to the specificity of mAb therapies, applications in neuro-ophthalmologic diseases have yielded exceptional clinical outcomes, including both reduced rate of relapse and progression to disability, visual function preservation, and quality of life improvement. These advancements have not only expanded the range of treatable neuro-ophthalmologic diseases but also reduced adverse events and increased the response rate to treatment. Further research into neuro-ophthalmologic disease mechanisms will provide accurate and specific targeting of important disease mediators through applications of future mAbs. As our understanding of these diseases and the relevant therapeutic targets evolve, we will continue to build on our understanding of how mAbs interfere with disease pathogenesis, and how these changes improve clinical outcomes and quality of life for patients.

Safety of Ambulatory Surgery For Obstructive Sleep Apnea: A Retrospective Review.

OBJECTIVE: Assess the safety of ambulatory surgery performed for obstructive sleep apnea. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care hospital. METHODS: Demographic data including age, gender, race, body mass index, insurance status, socioeconomic status, and distance traveled for surgery was collected, as well as comorbidities, and apnea-hypopnea index (AHI). Outcome variables included continuous positive airway pressure reinitiation, planned/unplanned postoperative admission, emergency department (ED) presentation, or readmission within 7 and 14 days of surgery. RESULTS: A total of 601 patients were included, who underwent sleep surgery between 2017 and 2022. The median age was 55 years [interquartile range: 19]. A total of 437 patients (73%) were male, 502 (84%) were Caucasian, and the median distance traveled was 20 miles [27]. The median AHI was 27.1 [26]. A total of 286 hypoglossal nerve stimulators, 12 tonsillectomies, 160 expansion sphincteroplasties (ESP), and 201 nasal procedures were performed. There were 9 (1%) planned and 23 (4%) total admissions postoperatively. Sixteen patients (2%) presented to ED within 7 days, and 22 (3%) within 14 days. Nine (1%) were readmitted within 7 days, and 12 (2%) within 14 days. There were significantly more planned admissions, unplanned admissions, ED presentations, and readmissions for ESP. There were no significant differences in demographic or clinical data between patients who underwent single versus multiple surgeries. CONCLUSION: Outpatient sleep surgery is generally safe. Close postoperative monitoring is necessary and overnight observation should be considered in those with very severe sleep apnea and/or significant comorbidities. The distance a patient travels should also be considered for overnight admission.

Rabies postexposure prophylaxis protocol option for unvaccinated domestic animals, Texas: 2010-2019.

OBJECTIVE: To assess data on rabies postexposure prophylaxis (PEP) in domestic animals following Texas' protocol and to describe preexposure and postexposure vaccination failures from 2010 through 2019. ANIMALS: 1,218 unvaccinated animals that received PEP, 925 unvaccinated animals that were euthanatized instead of receiving PEP, and 3 preexposure vaccinated dogs that developed rabies. METHODS: Zoonotic incident reports from 2010 through 2019 were reviewed for information regarding animals with no known rabies vaccination that received PEP or were euthanatized in accordance with state protocol after exposure to a laboratory-confirmed rabid animal; reports were also reviewed for any preexposure and postexposure vaccination failures. The state-required PEP protocol was to immediately vaccinate the animal against rabies, confine the animal for 90 days, and administer booster vaccines during the third and eighth weeks of the confinement period. RESULTS: From 2010 through 2019, 1,218 exposed animals received PEP; 99.8% did not develop rabies. Three failures were recorded, all in animals < 12 weeks of age when PEP was initiated. Additionally, 925 exposed animals were euthanatized instead of receiving PEP. One true preexposure vaccination failure was recorded. CLINICAL RELEVANCE: The Texas PEP protocol was used during the 10-year period. Results indicated that this protocol is a viable option for unvaccinated domestic animals exposed to rabies. Alternative protocols warrant additional consideration.

The ACE inhibitor captopril inhibits ACN-1 to control dauer formation and aging.

The renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan in Caenorhabditis elegans, Drosophila and rodents, but its mechanism is not well defined. Here, we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice. To investigate the mechanism, we performed a forward genetic screen for captopril-hypersensitive mutants. We identified a missense mutation that causes a partial loss of function of the daf-2 receptor tyrosine kinase gene, a powerful regulator of aging. The homologous mutation in the human insulin receptor causes Donohue syndrome, establishing these mutant worms as an invertebrate model of this disease. Captopril functions in C. elegans by inhibiting ACN-1, the worm homolog of ACE. Reducing the activity of acn-1 via captopril or RNA interference promoted dauer larvae formation, suggesting that acn-1 is a daf gene. Captopril-mediated lifespan extension was abrogated by daf-16(lf) and daf-12(lf) mutations. Our results indicate that captopril and acn-1 influence lifespan by modulating dauer formation pathways. We speculate that this represents a conserved mechanism of lifespan control.

Lymphocytic Panhypophysitis Mimicking Glaucoma: Case Report.

Lymphocytic hypophysitis (LH) is a primary inflammatory disorder of the pituitary gland and infundibulum that commonly manifests in both mass effect and endocrinologic symptoms. Although the exact pathophysiology remains unclear, it has been increasingly linked to an autoimmune process. Complications arise by two separate mechanisms. Inflammation in the sella can lead to headaches and visual field defects. Pituitary inflammation and, chronically, fibrosis interfere with the gland's hormone-secreting capacity, often resulting in various endocrinopathies such as polyuria, polydipsia, amenorrhea, and others. While final histologic classification requires pathologic evaluation, diagnosis can often be made clinically with appropriate imaging. Treatment often consists of conservative management but can also include glucocorticoids or surgical resection. We present a case of biopsy-proven LH involving the entire pituitary, dubbed lymphocytic panhypophysitis (LPH) that was misdiagnosed for years as glaucoma due to the lack of endocrinopathy as well as delay in magnetic resonance imaging. After imaging revealed the sellar mass, the patient responded symptomatically to surgical resection and glucocorticoid treatment. LPH may present without endocrinologic symptoms and therefore mimic alternate diagnoses such as glaucoma. Clinicians should be suspicious of a diagnosis of glaucoma in the setting of a temporal field defect and lack of response to traditional therapy. A personal or family history of autoimmune disease in such patients should prompt further imaging and investigation. Therefore, endocrinopathy is supportive but not present in every case of LPH.

The ACE-inhibitor drug captopril inhibits ACN-1 to control dauer formation and aging.

The renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan in C. elegans , Drosophila , and rodents, but its mechanism is not well defined. Here we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice. To investigate the mechanism, we performed a forward genetic screen for captopril hypersensitive mutants. We identified a missense mutation that causes a partial loss-of-function of the daf-2 receptor tyrosine kinase gene, a powerful regulator of aging. The homologous mutation in the human insulin receptor causes Donohue syndrome, establishing these mutant worms as an invertebrate model of this disease. Captopril functions in C. elegans by inhibiting ACN-1, the worm homolog of ACE. Reducing the activity of acn-1 via captopril or RNAi promoted dauer larvae formation, suggesting acn-1 is a daf gene. Captopril-mediated lifespan extension xwas abrogated by daf-16(lf) and daf-12(lf) mutations. Our results indicate that captopril and acn-1 control aging by modulating dauer formation pathways. We speculate that this represents a conserved mechanism of lifespan control. Summary Statement: Captopril and acn-1 control aging. By demonstrating they regulate dauer formation and interact with daf genes, including a new DAF-2(A261V) mutant corresponding to a human disease variant, we clarified the mechanism.

Predictors of postoperative performance status after surgical management of infratemporal fossa malignancies.

Infratemporal fossa (ITF) tumors are difficult to access surgically due to anatomical constraints. Moreover, aggressive ITF carcinomas and sarcomas necessitate aggressive treatment strategies that, along with tumor-related symptoms, contribute to decreases in patient performance status. To assess factors that predict postoperative performance in patients undergoing surgery for ITF tumors. We reviewed medical records for all patients surgically treated for an ITF malignancy between January 1, 1999, and December 31, 2017, at our institution. We collected patient demographics, preoperative performance, tumor stage, tumor characteristics, treatment modalities, pathological data, and postoperative performance data. The 5-year survival rate was 62.2%. Higher preoperative Karnofsky Performance Status (KPS) score (n = 64; p < 0.001), short length of stay (p = 0.002), prior surgery at site (n = 61; p = 0.0164), and diagnosis of sarcoma (n = 62; p = 0.0398) were predictors of higher postoperative KPS scores. Percutaneous endoscopic gastrostomy (PEG) (n = 9; p = 0.0327), and tracheostomy tube placement (n = 20; p = 0.0436) were predictors of lower postoperative KPS scores, whereas age at presentation (p = 0.72), intracranial tumor spread (p = 0.8197), and perineural invasion (n = 40; p = 0.2195) were not. Male patients and patients with carcinomas showed the greatest decreases in KPS scores between pretreatment and posttreatment. Higher preoperative KPS score and short length of stay were the best predictors of higher postoperative KPS scores. This work provides treatment teams and patients with better information on outcomes for shared decision-making.

Total Intravenous Anesthesia Versus Inhaled Sevoflurane in Obstructive Sleep Apnea Surgery: A Randomized Controlled Trial.

OBJECTIVE: Specific guidelines regarding an optimal general anesthesia (GA) approach to obstructive sleep apnea (OSA) patients remain undefined. Literature comparing the efficacy of total intravenous anesthesia (TIVA) and inhalational anesthesia in this population is sparse. We hypothesize that OSA patients receiving TIVA will experience reduced recovery times and other improved post-surgical outcomes. STUDY DESIGN: Randomized controlled trial. METHODS: Adult OSA patients undergoing upper airway surgery (hypoglossal nerve stimulation [HNS], nasal, or palate surgery) from February 2020-December 2020 were included. A post-anesthesia care unit (PACU) nursing survey documented patients' alertness, pain, oxygen supplementation, and postoperative nausea and vomiting from PACU arrival to 2 hours. Perioperative timepoints from the electronic medical record (EMR) and a nurse-estimated Phase I recovery time were collected. RESULTS: One hundred eleven patients were included (46 TIVA and 65 inhalational anesthesia). Per EMR-recorded timepoints, TIVA patients undergoing HNS and palate surgery experienced Phase I Time reductions of 12.5 min (p = 0.042) and 27.5 min (p = 0.016), respectively. Per the PACU survey, TIVA patients undergoing any surgery, HNS, or palate surgery experienced nurse-estimated Phase I Time reductions of 16.5 min (p = 0.004), 12.5 min (p = 0.031), and 38.5 min (p = 0.024), respectively. Overall, TIVA patients experienced higher alertness and pain ratings, and lower oxygen supplementation requirements from PACU arrival to 30 min (p < 0.05). CONCLUSION: Patients with OSA receiving TIVA for GA maintenance during upper airway procedures experienced reduced recovery times and oxygen supplementation requirements, and a more rapid return to alertness. Future work toward developing optimized anesthetic guidelines for OSA patients is merited. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:984-992, 2023.

Assessing Postoperative Recovery With Volatile Gas Versus Total Intravenous Anesthesia in Patients With and Without Obstructive Sleep Apnea.

INTRODUCTION: To determine if there is a recovery time difference between patients with and without obstructive sleep apnea (OSA) when using total intravenous anesthesia (TIVA) compared to volatile gas inhalational anesthesia. PATIENTS AND METHODS: OSA and Non-OSA patients were identified at a tertiary institution between January 2019 and November 2020. Non-OSA patients were defined as those who have not been formerly diagnosed with OSA. A modified STOP-BANG score (MSBS) was performed to screen Non-OSA patients for OSA. Recovery was measured by Phase I recovery time, or time it took a patient to reach ≥9/10 on the Aldrete scoring system. RESULTS: A total of 334 patients were included with 142 in the OSA cohort (59 TIVA, 83 inhalational anesthesia) and 192 in the Non-OSA cohort (119 TIVA, 73 inhalational anesthesia). In OSA patients, there was a 41.29-minute recovery time reduction when using TIVA versus sevoflurane (P < .0001). Non-OSA patients recovered faster than OSA patients when undergoing inhalational anesthesia by 46.76 minutes and TIVA by 18.58 minutes (P < .0001 and P = .0907, respectively). Non-OSA patients with a MSBS < 3 and ≥3 had a shorter recovery time compared to OSA patients when both underwent sevoflurane anesthesia (57.27 minutes, P < .0001 and 56.23 minutes, P = .040, respectively). Non-OSA patients with a MSBS of <3 had a decrease in recovery time of 26.68 minutes when compared to OSA patients who underwent TIVA (P = .0004). CONCLUSIONS: When utilizing TIVA over inhalational anesthesia, patients with OSA have significantly increased benefit in terms of reduced Phase I recovery times as compared to Non-OSA patients.

Activation of basal forebrain-to-lateral habenula circuitry drives reflexive aversion and suppresses feeding behavior.

Environmental cues and internal states such as mood, reward, or aversion directly influence feeding behaviors beyond homeostatic necessity. The hypothalamus has been extensively investigated for its role in homeostatic feeding. However, many of the neural circuits that drive more complex, non-homeostatic feeding that integrate valence and sensory cues (such as taste and smell) remain unknown. Here, we describe a basal forebrain (BF)-to-lateral habenula (LHb) circuit that directly modulates non-homeostatic feeding behavior. Using viral-mediated circuit mapping, we identified a population of glutamatergic neurons within the BF that project to the LHb, which responds to diverse sensory cues, including aversive and food-related odors. Optogenetic activation of BF-to-LHb circuitry drives robust, reflexive-like aversion. Furthermore, activation of this circuitry suppresses the drive to eat in a fasted state. Together, these data reveal a role of basal forebrain glutamatergic neurons in modulating LHb-associated aversion and feeding behaviors by sensing environmental cues.

Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology.

BACKGROUND: The management of sub-totally resected sporadic vestibular schwannoma (VS) may include observation, re-resection or irradiation. Identifying the optimal choice can be difficult due to the disease's variable progression rate. We aimed to define an immune signature and associated transcriptomic fingerprint characteristic of rapidly-progressing VS to elucidate the underpinnings of rapidly progressing VS and identify a prognostic model for determining rate of progression. METHODS: We used multiplex immunofluorescence to characterize the immune microenvironment in 17 patients with sporadic VS treated with subtotal surgical resection alone. Transcriptomic analysis revealed differentially-expressed genes and dysregulated pathways when comparing rapidly-progressing VS to slowly or non-progressing VS. RESULTS: Rapidly progressing VS was distinctly enriched in CD4+, CD8+, CD20+, and CD68+ immune cells. RNA data indicated the upregulation of anti-viral innate immune response and T-cell senescence. K - Top Scoring Pair analysis identified 6 pairs of immunosenescence-related genes (CD38-KDR, CD22-STAT5A, APCS-CXCR6, MADCAM1-MPL, IL6-NFATC3, and CXCL2-TLR6) that had high sensitivity (100%) and specificity (78%) for identifying rapid VS progression. CONCLUSION: Rapid progression of residual vestibular schwannoma following subtotal surgical resection has an underlying immune etiology that may be virally originating; and despite an abundant adaptive immune response, T-cell immunosenescence may be associated with rapid progression of VS. These findings provide a rationale for clinical trials evaluating immunotherapy in patients with rapidly progressing VS.

Advancements in the Quest to Map, Monitor, and Manipulate Neural Circuitry.

Neural circuits and the cells that comprise them represent the functional units of the brain. Circuits relay and process sensory information, maintain homeostasis, drive behaviors, and facilitate cognitive functions such as learning and memory. Creating a functionally-precise map of the mammalian brain requires anatomically tracing neural circuits, monitoring their activity patterns, and manipulating their activity to infer function. Advancements in cell-type-specific genetic tools allow interrogation of neural circuits with increased precision. This review provides a broad overview of recombination-based and activity-driven genetic targeting approaches, contemporary viral tracing strategies, electrophysiological recording methods, newly developed calcium, and voltage indicators, and neurotransmitter/neuropeptide biosensors currently being used to investigate circuit architecture and function. Finally, it discusses methods for acute or chronic manipulation of neural activity, including genetically-targeted cellular ablation, optogenetics, chemogenetics, and over-expression of ion channels. With this ever-evolving genetic toolbox, scientists are continuing to probe neural circuits with increasing resolution, elucidating the structure and function of the incredibly complex mammalian brain.

Co-transmitting neurons in the lateral septal nucleus exhibit features of neurotransmitter switching.

The lateral septal nucleus (LSN) is a highly interconnected region of the central brain whose activity regulates widespread circuitry. As such, the mechanisms that govern neuronal activity within the LSN have far-reaching implications on numerous brain-wide nuclei, circuits, and behaviors. We found that GABAergic neurons within the LSN express markers that mediate the release of acetylcholine (ACh). Moreover, we show that these vGATLSN neurons release both GABA and ACh onto local glutamatergic LSN neurons. Using both short-term and long-term neuronal labeling techniques we observed expression of the cholinergic neuron marker Choline Acetyltransferase (ChAT) in vGATLSN neurons. These findings provide evidence of cholinergic neurotransmission from vGATLSN neurons, and provide an impetus to examine dynamic co-neurotransmission changes as a potential mechanism that contributes to neuronal and circuit-wide plasticity within the LSN.

Cost of Total Intravenous Anesthesia Versus Inhalation Anesthesia in Obstructive Sleep Apnea Surgery.

OBJECTIVES: To compare cost and time spent in surgical and postoperative courses in patients with obstructive sleep apnea (OSA) undergoing surgery with either total intravenous anesthesia (TIVA) or inhalational anesthesia. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective review on patients undergoing surgery for OSA under general anesthesia from January 2019 to October 2020. Cost per service was acquired for the day of surgery. RESULTS: A total of 230 patients were included: 95 received TIVA; 135 received inhalation anesthesia. Total cost was significantly higher in the TIVA nasal surgery group by $286 (P = .035). TIVA produced significantly higher pharmacy and operating room costs across all surgeries and OSA severities. These increased costs were offset by significantly lower supply costs in upper airway stimulator (UAS, -$419.50; P = .007) and uvulopalatopharyngoplasty (UPPP, -$115.16; P = .015) patients receiving TIVA. In the TIVA cohort, there was a trend toward lower recovery room costs after UAS (-$111.09; P = .063) and nasal surgery (-$64.45; P = .096) and anesthesia costs after nasal surgery (-$36.67; P = .054). Total recovery time was reduced by 18 minutes (P = .004) for nasal surgery, 25 minutes (P = .043) for UAS, and 27 minutes (P = .147) for UPPP patients receiving TIVA. CONCLUSION: When used in an outpatient setting for patients with OSA, TIVA adds to pharmacy and operating room costs, but this is usually offset by lower supply, anesthesia, and recovery room costs. We found decreased recovery times in the TIVA cohort. TIVA has proven benefits in patient outcomes and can be cost-effective in OSA surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1487-1494, 2022.

A CRISPR toolbox for generating intersectional genetic mouse models for functional, molecular, and anatomical circuit mapping.

BACKGROUND: The functional understanding of genetic interaction networks and cellular mechanisms governing health and disease requires the dissection, and multifaceted study, of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic effector alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical studies. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, its experimental implementation has been broadly restricted to manipulations of a limited set of common alleles that are often commercially produced at great expense, with costs and technical challenges associated with production of intersectional mouse lines hindering customized approaches to many researchers. Here, we present a simplified CRISPR toolkit for rapid, inexpensive, and facile intersectional allele production. RESULTS: Briefly, we produced 7 intersectional mouse lines using a dual recombinase system, one mouse line with a single recombinase system, and three embryonic stem (ES) cell lines that are designed to study the way functional, molecular, and anatomical features relate to each other in building circuits that underlie physiology and behavior. As a proof-of-principle, we applied three of these lines to different neuronal populations for anatomical mapping and functional in vivo investigation of respiratory control. We also generated a mouse line with a single recombinase-responsive allele that controls the expression of the calcium sensor Twitch-2B. This mouse line was applied globally to study the effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on calcium release in the ovarian follicle. CONCLUSIONS: The lines presented here are representative examples of outcomes possible with the successful application of our genetic toolkit for the facile development of diverse, modifiable animal models. This toolkit will allow labs to create single or dual recombinase effector lines easily for any cell population or subpopulation of interest when paired with the appropriate Cre and FLP recombinase mouse lines or viral vectors. We have made our tools and derivative intersectional mouse and ES cell lines openly available for non-commercial use through publicly curated repositories for plasmid DNA, ES cells, and transgenic mouse lines.

Oxytocin signaling is necessary for synaptic maturation of adult-born neurons.

Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial and temporal enrichment of oxytocin receptor expression within adult-born neurons in the murine olfactory bulb, with oxytocin receptor expression peaking during activity-dependent integration. Using viral labeling, confocal microscopy, and cell type-specific RNA-seq, we demonstrate that oxytocin receptor signaling promotes synaptic maturation of newly integrating adult-born neurons by regulating their morphological development and expression of mature synaptic AMPARs and other structural proteins.

Imaging and Quantification of Intact Neuronal Dendrites via CLARITY Tissue Clearing.

Brain activity, the electrochemical signals passed between neurons, is determined by the connectivity patterns of neuronal networks, and from the morphology of processes and substructures within these neurons. As such, much of what is known about brain function has arisen alongside developments in imaging technologies that allow further insight into how neurons are organized and connected in the brain. Improvements in tissue clearing have allowed for high-resolution imaging of thick brain slices, facilitating morphological reconstruction and analyses of neuronal substructures, such as dendritic arbors and spines. In tandem, advances in image processing software provide methods of quickly analyzing large imaging datasets. This work presents a relatively rapid method of processing, visualizing, and analyzing thick slices of labeled neural tissue at high-resolution using CLARITY tissue clearing, confocal microscopy, and image analysis. This protocol will facilitate efforts toward understanding the connectivity patterns and neuronal morphologies that characterize healthy brains, and the changes in these characteristics that arise in diseased brain states.

A systematic-review of olfactory deficits in neurodevelopmental disorders: From mouse to human.

Olfactory impairment is a common clinical motif across neurodevelopmental disorders, suggesting olfactory circuits are particularly vulnerable to disease processes and can provide insight into underlying disease mechanisms. The mouse olfactory bulb is an ideal model system to study mechanisms of neurodevelopmental disease due to its anatomical accessibility, behavioral relevance, ease of measuring circuit input and output, and the feature of adult neurogenesis. Despite the clinical relevance and experimental benefits, olfactory testing across animal models of neurodevelopmental disease has been inconsistent and non-standardized. Here we performed a systematic literature review of olfactory function testing in mouse models of neurodevelopmental disorders, and identified intriguing inconsistencies that include evidence for both increased and decreased acuity in odor detection in various mouse models of Autism Spectrum Disorder (ASD). Based on our identified gaps in the literature, we recommend direct comparison of different mouse models of ASD using standardized tests for odor detection and discrimination. This review provides a framework to guide future olfactory function testing in mouse models of neurodevelopmental diseases.