JNeurosci publishes a broad spectrum of articles reporting important work across areas of neuroscience. Because keeping up with exciting work outside your individual subdiscipline can be difficult, JNeurosci created the Spotlight feature to highlight articles that our reviewers gave the highest marks for both methodological merit and significance. We hope the papers in this year’s Spotlight will be of interest to neuroscientists across areas and at many different levels of experience. Below is the collection of this year’s Spotlight papers and summaries of their key findings. Papers selected for the Spotlight feature in previous years can be found below as well.
2024
Behavioral/Cognitive
Investigating Egocentric Tuning in Hippocampal CA1 Neurons
During navigation, the hippocampus integrates egocentric (self-centered) and allocentric (world-centered) information to build a mental map of an organism’s position in space. Some studies show that hippocampal place cells, which encode allocentric data, may be tuned by egocentric coding. But this study by Carpenter et al. looked at experimental and simulated hippocampal single-unit recording data as rats foraged in an open field and revealed that while there is some evidence of internal egocentric signals regulating place cell activity, there are many false positives.
Behavioral/Cognitive
Oculomotor Contributions to Foveal Crowding
Visually focusing on an individual object becomes difficult in a crowded scene. Previous work investigating why this phenomenon occurs has focused on how visual crowding affects peripheral vision, but Clark et al. extended our understanding by investigating how visual crowding influences human foveal vision. The authors used high-precision eye tracking and retinal stabilization tools to reveal that fixational eye movements worsen visual crowding effects on foveal vision, which counters previous observations with peripheral vision. This finding suggests that visual crowding mechanisms differ for foveal and peripheral vision.
Cellular/Molecular
Fast Inhibition Slows and Desynchronizes Mouse Auditory Efferent Neuron Activity
Perceiving sounds requires quick, precise neural responses to distinct sound features. Auditory neurons in the cochlear nucleus (CN) and brainstem process these signals and medial olivocochlear (MOC) neurons provide inhibition in the cochlea to support this CN neuron processing of sound. But because MOC neurons modulate the cochlea on a slow timescale, Fischl et al. explored whether there are mechanisms that reduce MOC inhibition to promote auditory neuron speed and precision. Using an in vitro slice preparation, they discovered that inhibition of the MOC is fast with variable onset when localized to the CN. This variable onset delays and desynchronizes MOC activity, potentially ensuring that the MOC does not inhibit the cochlea during rapid sounds and is only engaged during slower, more sustained background sounds.
Cellular/Molecular
Atp13a5 Marker Reveals Pericyte Specification in the Mouse Central Nervous System
Because pericytes have broad expression in the body and exhibit genetic overlap with other cell types, it is difficult to explore the distinct role of central nervous system (CNS) pericytes in health and disease. Guo and colleagues overcame this hurdle in mice by developing a genetic mouse line after identifying the Atp13a5 gene as specific to CNS pericytes. This mouse line allowed the authors to investigate the timescale of CNS pericyte expression and they discovered that these pericytes are detectable at the point in which the blood–brain barrier becomes functional. They also found evidence that environmental cues influence CNS pericyte specialization.
Development/Plasticity/Repair
Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo
Most genetic hearing loss is caused by problems with cochlear inner hair cells (IHCs) and outer hair cells (OHCs). Exploring mechanisms of hair cell development may inform treatment strategies for hair cell regeneration. Research shows that Tbx2 is expressed in IHCs but is dampened in OHCs and that OHCs with Tbx2 may convert into IHC-like cells. But how rampantly this change occurs and the mechanisms driving it were unknown prior to this investigation by Bi and colleagues. Researchers used a mouse model to discover that Tbx2 overexpression in neither neonatal OHCs nor cochlear progenitors led to complete transitions into IHCs. Restoring an OHC gene that was downregulated after Tbx2 overexpression (Ikzf2) minimized abnormal OHC formation, suggesting that Ikzf2 repression may underlie OHC transitions into IHC-like cells.
Development/Plasticity/Repair
Oligodendrocyte Maturation Alters the Cell Death Mechanisms That Cause Demyelination
Oligodendrocyte death and axon demyelination contribute to age-related cognitive decline. In their article, Chapman et al. emphasize the importance of considering oligodendrocyte maturation state when designing treatment strategies to preserve cognition by limiting oligodendrocyte death and axon demyelination. Using intravital imaging, single-cell ablation, and cuprizone-mediated demyelination, Chapman et al. discovered that precursor cells, differentiating oligodendrocytes, and mature oligodendrocytes have distinct mechanisms underlying their deaths, which also occur at different rates.
Systems/Circuits
Cone-Opponent Ganglion Cells in the Primate Fovea Tuned to Noncardinal Color Directions
How retinal ganglion cells (RGCs) combine the three cone photoreceptor types (long, medium, and short wavelength sensitive) to enable color perception is unclear. Cone photoreceptors combine along opposing axes to allow perception of red–green or blue–yellow hues. The cone opponency underlying these axes may be established in the cortex, but Godat et al. investigated whether these signals are also present in the eye. The authors performed adaptive optics calcium imaging to measure nonhuman primate RGC light responses and found more diverse color signals in the retina than previously thought.
Systems/Circuits
Oscillatory Waveform Shape and Temporal Spike Correlations Differ across Bat Frontal and Auditory Cortex
The waveform shape of oscillatory cortical activity provides insight into aberrant or dynamic behavioral states. This paper by García-Rosales and colleagues sheds more light on the physiological properties of neural oscillations in auditory and frontal areas in awake male bats. Using simultaneous recordings of local field potentials from these brain areas, the authors found that oscillatory waveform shape differs in fronto-auditory cortical regions during spontaneous neural activity. The idea that oscillatory activity in frontal and auditory cortex distinctly relates to the anatomical and functional diversity of the fronto-auditory circuit is informative for the field.
Neurobiology of Disease
Neural Network Connectivity Following Opioid Dependence is Altered by a Common Genetic Variant in the µ-Opioid Receptor, OPRM1 A118G
A common single nucleotide polymorphism in the µ-opioid receptor gene is associated with opioid addiction susceptibility, but its effect on the brain network that mediates opioid abuse is unknown. To explore this effect, Xie and colleagues probed neuronal network–level activity differences between opioid-naive and opioid-dependent mice. They discovered sex- and genotype-specific modifications in neural networks from opioid exposure. This study points to potential brain regions for noninvasive and personalized therapeutic approaches.
Neurobiology of Disease
TSG-6–Mediated Extracellular Matrix Modifications Regulate Hypoxic–Ischemic Brain Injury
Extracellular matrix modification contributes to hypoxic–ischemic brain injury, which is a common cause of morbidity and mortality. However, mechanistic insight is lacking. Srivastava and colleagues used mice to examine the role of extracellular matrix regulation in this kind of brain injury and revealed that a key regulator of age- and sex-dependent hypoxic–ischemic injury responses in the mouse brain is modulation of the Hippo-yes–associated protein 1 pathway by TNF-stimulated gene-6–dependent extracellular matrix modifications.
2023
Behavioral/Cognitive
Structural Fingerprinting of the Frontal Aslant Tract: Predicting Cognitive Control Capacity and Obsessive-Compulsive Symptoms
The frontal aslant tract allows communication between brain regions that regulate the processing of new information and the control of reflexive behaviors. The connectivity of these regions is thought to be uniquely individual, but the individuality of the frontal aslant tract and its role in cognitive control were unknown prior to this rigorous human imaging study by Wang and colleagues. They used multiple datasets and complementary analyses to discover that the frontal aslant tract is a structural fingerprint of the brain capable of predicting cognitive control and obsessive-compulsive disorder severity.
Listen to Danni Wang, Yihong Yang, and Yao Li discuss their paper on Episode 33 of Neuro Current: An SfN Journals Podcast. 
Behavioral/Cognitive
Spontaneous α Brain Dynamics Track the Episodic “When”
A major component of our understanding of reality is the feeling that time passes, which requires tracking the passage of time. A century-old working hypothesis suggests our “internal clocks” are driven by brain activity called “alpha” rhythms. Azizi et al. explored this link more directly by using magnetoencephalography to record from human brains under two time-tracking behavioral conditions. They discovered that the bursting time of alpha rhythms reliably indicated how much time an individual would report to having elapsed, but that alpha wave time tracking vanished when individuals predicted the amount of time and were attending to it during recording. This novel link between oscillatory bursts and spontaneous cognition may shape the direction of study for this field of research.
Listen to Leila Azizi, Ignacio Polti and Virginie van Wassenhove discuss their paper on Episode 34 of Neuro Current: An SfN Journals Podcast. 
Cellular/Molecular
Selective Serotonin Reuptake Inhibitors within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and Membrane
Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine and escitalopram, are given to millions of people for mood stabilization. It is assumed that these therapeutic drugs increase extracellular serotonin levels by inhibiting the transporter that clears serotonin from synapses. However, the biophysical mechanism of SSRIs may be more complex than that. In this study, Nichols et al. developed novel tools to investigate the accumulation and kinetics of fluoxetine and escitalopram in different cellular compartments, using both primary neurons and neuronal cell lines for their observations. Their findings may inform future exploration on where and how SSRIs engage therapeutic targets.
Listen to Aaron Nichols discuss his paper on Episode 27 of Neuro Current: An SfN Journals Podcast. 
Cellular/Molecular
GRM2 Regulates Functional Integration of Adult-Born DGCs by Paradoxically Modulating MEK/ERK1/2 Pathway
Dentate granule cells (DGCs) that develop in adulthood form hippocampal neural circuits that serve major roles in regulating memories, moods, and emotions. If DGCs do not properly form and integrate into circuits, diseases such as schizophrenia, epilepsy, and Alzheimer’s can occur. But the mechanisms by which this happens are unknown. Ma and colleagues used in vivo and in vitro experiments to investigate the role of metabotropic glutamate receptor 2 (GRM2), which is highly expressed on mature DGCs, in aberrant development and integration of adult-born DGCs into circuits. They discovered a unique time course of GRM2 expression in adult-born neurons that is necessary for neuron development and memory and identified intrinsic regulatory signaling that may be targeted with pharmacological treatments.
Developmental/Plasticity/Repair
Structural Preservation Does Not Ensure Function at Sensory Ia–Motoneuron Synapses following Peripheral Nerve Injury and Repair
Damage to peripheral nerves can cause permanent deficits in motor behavior due to irreversible reorganization of spinal circuitry. Even nerve regeneration does not reverse the damage. Rotterman et al. investigated whether the damage from peripheral injury can be attributed to inflammatory immune responses. They used an anti-inflammatory agent to prevent the immune response following an experimental model of peripheral nerve damage in rats and found that, while this prevented the physical loss of peripheral nerve-motoneuron synapses, it did not overcome the functional decline of synapses. The idea that synaptic structure and function are dissociable is a breakthrough in our understanding of nerve injury and repair.
Development/Plasticity/Repair
Notch Signaling Plays a Dual Role in Regulating the Neuron-to-Oligodendrocyte Switch in the Developing Dorsal Forebrain
The timing of neurodevelopmental processes is critical. It is known that neural progenitors make oligodendrocytes after neurons, but Tran et al. used in utero electroporation to investigate the mechanisms that drive the timing of this switch. They discovered that Notch signaling has dual roles in regulating progenitor quantity and oligodendrocyte production that are driven by discrete mechanisms: it is required to form oligodendrocytes, but elevated Notch signaling prevents oligodendrogenesis and maintains a progenitor state. This study underscores the complexity of the Notch pathway and reveals its necessity in regulating cell production during cortical development.
Neurobiology of Disease
NMDA Receptors at Primary Afferent–Excitatory Neuron Synapses Differentially Sustain Chemotherapy- and Nerve Trauma-Induced Chronic Pain
Cancer chemotherapeutics and peripheral nerve injury are major contributors to chronic pain, or pain hypersensitivity. Pain hypersensitivity is associated with glutamatergic NMDA receptors in the spinal dorsal horn, but this study by Huang et al. delineates the different NMDA mechanisms in chemotherapy- and nerve injury-induced neuropathic pain. While both chemotherapy and traumatic nerve injury preferentially enhance NMDA activity at excitatory neuron synapses, pre- and post-synaptically expressed NMDA receptors have separate roles in chemotherapy- and nerve injury-induced pain behaviors. These findings may aid in identifying more specific treatment targets for these discrete conditions.
Neurobiology of Disease
Differential Patterns of Synaptic Plasticity in the Nucleus Accumbens Caused by Continuous and Interrupted Morphine Exposure
Continued exposure to and withdrawal from drugs of abuse causes adaptations in brain circuits that contribute to addiction. Understanding the neurobiological changes that occur during opioid addiction is difficult because the changes can vary depending on the nature of exposure. Lefevre et al. approached this challenge by manipulating the pattern of opioid (more specifically, morphine) exposure while measuring cellular and synaptic adaptations of the output neurons of the integration center for reward circuits in the brain: the nucleus accumbens. They found that communication between neurons changed in distinct ways depending on whether morphine administration was continuous or interrupted. Some changes also varied depending on neuron subtype and sex.
Listen to Emilia Lefevre discusses her paper on Episode 28 of Neuro Current: An SfN Journals Podcast. 
Systems/Circuits
Subgenual and Hippocampal Pathways in Amygdala Are Set to Balance Affect and Context Processing
Learning, memory, and emotions rely on activity in the hippocampus, subgenual cortex area 25 (A25), and basolateral amygdala (BLA). But pathway interactions between the hippocampus and A25, which innervate the BLA, or the cellular targets of these projections in the BLA are not well described. This anatomical nonhuman primate study by Joyce and colleagues details patterns of terminal innervations and includes quantitative mapping of projections onto putative excitatory and inhibitory neurons of different subtypes. The functional significance of these data is also discussed, especially as it pertains to complex emotional and reward processing behaviors. The common and unique patterns of innervation described indicate how these complex behaviors may be selectively disrupted in psychiatric disorders.
Listen to Mary Kate Joyce discusses her paper on Episode 29 of Neuro Current: An SfN Journals Podcast. 
Systems/Circuits
Interchangeable Role of Motor Cortex and Reafference for the Stable Execution of an Orofacial Action
For many animals, whiskers are critical for sensing their surroundings and navigating their environments. Properly making use of whiskers requires tracking their positioning, but how animals do this is underexplored. Elbaz et al. measured rat whisker movement and the mechanisms of motor control in their study. They found that proper whisker positioning required the presence of either sensory feedback (also known as peripheral reafference) or motor cortex – it was only when both were absent that voluntary motion and precision were sacrificed. Thus, organisms use both motor cortex and peripheral reafference to track their position in space.
Listen to Michaël Elbaz discusses his paper on Episode 32 of Neuro Current: An SfN Journals Podcast. 2022
JUN Regulation of Injury-Induced Enhancers in Schwann Cells
Listen to Raghu Ramesh and John Svaren discuss their paper on Episode 21 of Neuro Current: An SfN Journals Podcast.Temporal Dynamics of Neural Responses in Human Visual Cortex
Listen to Iris Groen discuss her paper on Episode 22 of Neuro Current: An SfN Journals Podcast. Listen to Anan Moran and Elor Arieli discuss their paper on Episode 20 of Neuro Current: An SfN Journals Podcast.