Material below is adapted from the SfN Short Course, Adult Mouse Cortical Cell Taxonomy Revealed by Single-Cell Transcriptomics, by Bosiljka Tasic, PhD. Short Courses are day-long scientific trainings on emerging neuroscience topics and research techniques held just prior to SfN’s annual meeting. Single-cell RNA sequencing (RNA-seq) is a powerful tool that can help researchers look more deeply at individual cells, in order to better understand differences within tissues or groups of cells. One research team used RNA-seq to classify more than 1,600 cells from the cortex of adult male mice.

Transgenic mice provide unprecedented access to manipulate and visualize neural circuits, however, those on a C57BL/6 background develop progressive hearing loss, significantly confounding systems-level and behavioral analysis. While outbreeding can limit hearing loss, it introduces strain variability and complicates the generation of complex genotypes. Here, we propose an approach to preserve hearing by crossing transgenic mice with congenic B6.CAST- Cdh23Ahl+ mice, which maintain low-threshold hearing into adulthood. Widefield and two-photon imaging of the auditory cortex revealed that 2.5-month-old C57BL/6 mice exhibit elevated thresholds to high frequency tones and widespread cortical reorganization, with most neurons responding best to lower frequencies. In contrast, Ahl+ C57BL/6 mice exhibited robust neural responses across tested frequencies and sound levels (4-64 kHz, 30-90 dB SPL) and retained low thresholds into adulthood. Our approach offers a cost-effective solution for generating complex genot...

Growth hormone (GH) is a neuromodulator that binds to receptors in the hippocampus and alters synaptic plasticity. Decline in GH levels is associated with normal ageing, stress and disease, and mechanisms proposed involve the hippocampal circuit plasticity. To see how GH affects the hippocampal neural code, we recorded single neurons in the CA1 region of male Long Evans rats with locally altered GH levels. Rats received injections of adeno-associated viruses into the hippocampus to make the cells overexpress either GH or an antagonizing mutated GH (aGH). Place cells were recorded in both familiar and novel environments to allow the assessment of pattern separation in the neural representations termed remapping. All the animals showed intact and stable place fields in the familiar environment. In the novel environment, aGH transfection increased the average firing rate, peak rate and the information density of the CA1 place fields. The tendency of global remapping increased in the GH animals compared to the...

The adrenal medulla is packed with chromaffin cells, modified postganglionic sympathetic neurons that secrete the catecholamines, epinephrine and norepinephrine, during the fight-or-flight response. Sometimes overlooked, is a population of immune cells that also resides within the gland but whose distribution and function is not clear. Here I examine the location of CD45+ hematopoietic cells in the mouse adrenal medulla and show the majority are F4/80+/Lyz2+ macrophages. These cells are present from early post-natal development and widely distributed. Anatomically they are associated with chromaffin cells, found aligned alongside synapsin-ir neuronal varicosities and juxtaposed to CD31-ir blood vessels. Using Lyz2cre-GCaMP6f mice to quantify calcium signaling in macrophages revealed these cells respond directly and indirectly to a wide variety of neuromodulators, including pre- and post-ganglionic transmitters and systemic hormones. Purinergic agonists, histamine, acetylcholine and bradykinin rapidly and r...

Phillip West is an assistant professor of microbial pathogenesis and immunology at the Texas A&M University Health Science Center. He led a breakout group at the 2016 Neurobiology of Disease Workshop, From Pediatric Encephalopathy to Alzheimer's: Linking Mitochondria to Neurological Diseases, and presented in 2017 follow-up webinar, Linking Mitochondria to Neurological Disease. Here, he shares what led him to this research path and why it excites him. As told to, and edited by, SfN staff.

Material below is adapted from the SfN Short Course, Transcription Dysregulation of the PGC-1α Pathway in Huntington’s Disease Pathogenesis: From Metabolic Derangement to Neurodegeneration, by Albert R. La Spada, MD, PhD.

Speech intelligibility declines with age and sensorineural hearing damage (SNHL). However, it remains unclear whether cochlear synaptopathy (CS), a recently discovered form of SNHL, significantly contributes to this issue. CS refers to damaged auditory-nerve synapses that innervate the inner hair cells and there is currently no go-to diagnostic test available. Furthermore, age-related hearing damage can comprise various aspects (e.g., hair cell damage, CS) that each can play a role in impaired sound perception. To explore the link between cochlear damage and speech intelligibility deficits, this study examines the role of CS for word recognition among older listeners. We first validated an envelope-following response (EFR) marker for CS using a Budgerigar model. We then applied this marker in human experiments, while restricting the speech material’s frequency content to ensure that both the EFR and the behavioral tasks engaged similar cochlear frequency regions. Following this approach, we identified the ...

The use of supervised machine learning to approximate poses in video recordings allows for rapid and efficient analysis of complex behavioral profiles. Currently, there are limited protocols for automated analysis of operant self-administration behavior. We provide a methodology to (1) obtain videos of training sessions via Raspberry Pi microcomputers or GoPro cameras, (2) obtain pose estimation data using the supervised machine learning software packages DeepLabCut (DLC) and Simple Behavioral Analysis (SimBA) with a local high-performance computer cluster, (3) compare standard Med-PC lever response versus quadrant time data generated from pose estimation regions of interest, and (4) generate predictive behavioral classifiers. Overall, we demonstrate proof of concept to use pose estimation outputs from DLC to both generate quadrant time results and obtain behavioral classifiers from SimBA during operant training phases.

Food intake is controlled by multiple converging signals: hormonal signals that provide information about energy homeostasis and hedonic and motivational aspects of food and food cues that can drive nonhomeostatic or “hedonic” feeding. The ventral pallidum (VP) is a brain region implicated in the hedonic and motivational impact of food and food cues, as well as consumption of rewards. Disinhibition of VP neurons has been shown to generate intense hyperphagia, or overconsumption. While VP GABA neurons have been implicated in cue-elicited reward-seeking and motivation, the role of these neurons in the hyperphagia resulting from VP activation remains unclear. Here, we used designer receptors exclusively activated by designer drugs to activate VP GABA neurons in nonrestricted male and female rats during chow and sucrose consumption. We found that activation of VP GABA neurons increases consumption of chow and sucrose in male rats, but not female rats. Together, these findings suggest that activation of VP GABA...

Chronic pain is a debilitative disease affecting one in five adults globally and is a major risk factor for anxiety ( [Goldberg and McGee, 2011][1]; [Lurie, 2018][2]). Given the current dearth of available treatments for both individuals living with chronic pain and mental illnesses, there is a critical need for research into the molecular mechanisms involved in order to discover novel treatment targets. Cellular homeostasis is crucial for normal bodily functions, and investigations of this process may provide better understanding of the mechanisms driving the development of chronic pain. Using the spared nerve injury (SNI) model of neuropathic pain, we found contrasting roles for BECLIN-1 in the development of pain hypersensitivity and anxiety-like behaviors in a sex-dependent manner. Remarkably, we found that male SNI mice with impaired BECLIN-1 function demonstrated heightened mechanical and thermal hypersensitivity compared with male wild-type SNI mice, while female SNI mice with impaired BECLIN-1 func...