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.

The perception of scenes is associated with processing in a network of scene-selective regions in the human brain. Prior research has identified a posterior–anterior bias within this network. Posterior scene regions exhibit preferential connectivity with early visual and posterior parietal regions, indicating a role in representing egocentric visual features. In contrast, anterior scene regions demonstrate stronger connectivity with frontoparietal control and default mode networks, suggesting a role in mnemonic processing of locations. Despite these findings, evidence linking connectivity in these regions to cognitive scene processing remains limited. In this preregistered study, we obtained cognitive behavioral measures alongside resting-state fMRI data from a large-scale public dataset to investigate interindividual variation in scene processing abilities relative to the functional connectivity of the scene network. Our results revealed substantial individual differences in scene recognition, spatial mem...

Functional ultrasound (fUS) imaging is a well-established neuroimaging technology that offers high spatiotemporal resolution and a large field of view. Typical strategies for analyzing fUS data comprise either region-based averaging, typically based on reference atlases, or correlation with experimental events. Nevertheless, these methodologies possess several inherent limitations, including a restricted utilization of the spatial dimension and a pronounced bias influenced by preconceived notions about the recorded activity. In this study, we put forth single-voxel clustering as a third method to address these issues. A comparison was conducted between the three strategies on a typical dataset comprising visually evoked activity in the superior colliculus in awake mice. The application of single-voxel clustering yielded the generation of detailed activity maps, which revealed a consistent layout of activity and a clear separation between hemodynamic responses. This method is best considered as a complement...

The role of sleep in memory consolidation is a widely discussed but still debated area of research. In light of the fact that memory consolidation during sleep is an evolutionary adaptive function, investigating the same phenomenon in nonhuman model species is highly relevant for its understanding. One such species, which has acquired human-analog sociocognitive skills through convergent evolution, is the domestic dog. Family dogs have surfaced as an outstanding animal model in sleep research, and their learning skills (in a social context) are subject to sleep-dependent memory consolidation. These results, however, are correlational, and the next challenge is to establish causality. In the present study, we aimed to adapt a TMR (targeted memory reactivation) paradigm in dogs and investigate its effect on sleep parameters. Dogs ( N  = 16) learned new commands associated with different locations and afterward took part in a sleep polysomnography recording when they were re-exposed to one of the previously l...

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 ...