Protein tyrosine phosphatase receptor type Z1 ( Ptprz1 ) is one of the most abundantly expressed and enriched genes in astrocytes during development, yet its function in astrocytes is unknown. Using an astrocyte–neuron coculture system, we found that knockdown of Ptprz1 in astrocytes significantly impaired astrocyte branching morphogenesis. To investigate the function of Ptprz1 in astrocytes during brain development, we generated a Ptprz1 conditional knock-out mouse and deleted Ptprz1 from astrocytes postnatally, after the bulk of astrogenesis is complete. At postnatal day 21, we found subtle changes in astrocyte morphology and a reduction in the density of colocalized pre- and postsynaptic excitatory synapse markers across multiple layers of the visual cortex in both male and female mice, suggesting important functions for astrocytic Ptprz1 in both astrocyte morphogenesis and synaptogenesis. Ptprz1 is expressed in several neural cell types, including radial glial stem cells and oligodendrocyte progenitor ...

Cortical neurons in sensory areas undergo a protracted process of postnatal maturation that includes changes in membrane properties, synaptic drive, and connectivity. The completion of this process is associated with the closure of critical periods for experience-dependent plasticity in visual, auditory, and somatosensory cortices. Whether these findings extend to the postnatal development of cortical circuits for taste is currently unknown. Taste receptor cells in the taste buds reliably fire action potentials in response to taste stimuli by the third postnatal week and show extended refinement of membrane excitability into adulthood. Taste responsive neurons in the nucleus of the solitary tract show reorganization of peripheral nerve terminals (NTS) over a timeline comparable to taste buds. However, no study to date investigated the postnatal development of neurons in the gustatory cortex (GC). Here, we focused on pyramidal neurons in the deep layers of GC in acute slices from male and female mice and co...

Accurate characterization of auditory pathway responses is critical for understanding neural disorders that affect hearing, including both peripheral and central deficits, as well as broader neurodevelopmental conditions. Animal models provide a way to investigate auditory circuit activation with high spatial and temporal resolution. Here, we first assessed behavioral detection of pure tones (PT) and narrowband noise (NBN) stimuli in male rats, revealing that NBN targets were detected at lower amplitudes than PT targets, consistent with human auditory detection patterns. We then compared these behavioral results with neural responses recorded in female rats’ medial geniculate body (MGB), a thalamic relay to the auditory cortex. Using high-density multichannel recordings, we found that NBN stimuli elicited greater neural sensitivity at low amplitudes, whereas PT stimuli evoked faster responses and higher peak firing rates. MGB units achieved maximal frequency discrimination at amplitudes close to detection ...

Elucidating the neural substrates of pavlovian reward learning requires reliable behavioral readouts. In conditioned magazine approach studies, rodents express reward expectancy by approaching the food magazine during cues that predict reward. This behavior is typically quantified using one of three measures: number of head entries, percentage of time in the magazine, or latency to respond. Yet these measures often diverge within the same discrimination task, making reliance on a single metric problematic. At the individual level, some animals express discrimination learning most clearly in one measure while showing little or no learning in the others, and animals may even switch their preferred measure across training. Reporting only one measure therefore risks underestimating the ability of a subset of animals. At the group level, sampling error can produce apparent differences across replications of the same design, limiting replicability. Moreover, brain manipulations can alter response topography, suc...

Extinction-reinstatement paradigms have been used to study reward-seeking for both food and drug rewards. The nucleus accumbens (NAc) is of particular interest in reinstatement due to its ability to energize motivated behavior. Previous work found that suppression of neuronal activity or dopamine signaling in NAc reduces reinstatement of food-seeking. Here we used fiber photometry and sensor multiplexing (red-shifted dopamine sensor and genetically-encoded calcium indicator) to measure dopamine and calcium in NAc core of male and female rats on each day of an extinction-reinstatement paradigm with food reward to determine how signals vary across task phases. During self-administration training, we detected positive dopamine transients that initially followed lever pressing but moved earlier in time as training progressed. A post-press dopamine decrease also emerged with training. For calcium, a decrease from baseline occurred after the press and became more prominent across training. Both patterns were red...

The flexible control of working memory (WM) requires prioritizing immediately task-relevant information while maintaining information with potential future relevance in a deprioritized state. Using double-serial retrocuing (DSR) with simultaneous EEG recording, we investigated how single pulses of transcranial magnetic stimulation (spTMS) to right intraparietal sulcus impacts neural representations of unprioritized memory items (UMI), relative to irrelevant memory items (IMI) that are no longer needed for the trial. Twelve human participants (8 female) performed DSR plus a single-retrocue task, while spTMS was delivered during delay periods. Multivariate pattern analysis revealed that spTMS restored decodability of the UMI concurrent with stimulation and that of the IMI several timesteps later, after the evoked effects of spTMS were no longer present in the EEG signal. This effect was carried by the alpha (8–13 Hz) and low-beta (13–20 Hz) frequency bands. Analyses of the raw EEG signal showed two effects s...

Despite advances in brain–computer interfaces, decoding high-level language representations prior to speech remains challenging. While prior efforts have focused on acoustic or articulatory features, how semantic categories are decoded in time and space remains unclear. Here, we investigated how semantic representations unfold over time by analyzing high-gamma (HG; 70–170 Hz) electrocorticography signals from 20 subjects (7 females and 13 males) performing a word-reading task with body- and nonbody-related words. HG activity was examined from word presentation to 500 ms. Group-level time–resolved decoding within each Brodmann area (BA) revealed significant classification accuracy above chance in both hemispheres ( p  < 0.05, FDR-corrected). In the left hemisphere, peak BAs followed a frontal–temporal–occipital–parietal cascade: dorsolateral prefrontal cortex (dlPFC; 50 ms), inferior temporal and fusiform gyri (350–400 ms), and supramarginal gyrus (SMG; 500 ms). In contrast, the right hemisphere exhibited a...

Spiking thresholds in neurons or rectification at synapses are essential for neuronal computations rendering neuronal processing inherently nonlinear. Nevertheless, linear response theory has been instrumental for understanding, for example, the impact of noise or neuronal synchrony on signal transmission, or the emergence of oscillatory activity, but is valid only at low stimulus amplitudes or large levels of intrinsic noise. At higher signal-to-noise ratios, however, nonlinear response components become relevant. Theoretical results for leaky integrate-and-fire neurons in the weakly nonlinear regime suggest strong responses at the sum of two input frequencies if one of these frequencies or their sum match the neuron’s baseline firing rate. We here analyze nonlinear responses in two types of primary electroreceptor afferents, the P-units of the active and the ampullary cells of the passive electrosensory system of the wave-type electric fish Apteronotus leptorhynchus of either sex. In our combined experim...

Stressful events are a leading factor in the development of depression. The medial prefrontal cortex (mPFC) is strongly associated with depression etiology and exposure to uncontrollable stressors results in synaptic dysfunction and loss. Learned helplessness is a behavioral paradigm that measures effects of repeated exposure to uncontrollable, inescapable stress on later responses to escapable stress. We therefore performed a proteomic analysis of mPFC synaptosomes in a mouse learned helplessness model to identify molecular changes that could contribute to functional consequences of inescapable stress. Male and female mice were evaluated at baseline and following exposure to escapable or inescapable stress followed by an active avoidance test. Label-free mass spectrometry followed by pathway and protein–protein interaction network analyses identified alterations in signaling pathways involved in energy metabolism, neurotransmitter signaling, and protein shuttling. Furthermore, phosphoproteomics revealed a...

Age-related alterations in myelin are a prominent feature of brain aging, yet how myelin-associated markers and oligodendrocyte lineage cell populations change across the primate lifespan remains incompletely characterized. Here, we provide a multimodal, cross-sectional analysis of myelin-related imaging and cellular markers in the prefrontal cortex (PFC) of age-matched both male and female rhesus macaques across postnatal development and aging using a multimodal approach combining magnetic resonance imaging (MRI), histological analysis, immunohistochemistry, and RNAscope in situ hybridization. We quantified regional gray and white matter volumes and myelin water fraction measures in prefrontal cortex (PFC) subregions BA9 and BA46 across four age groups: 5, 10, 15, and 30 years. Myelin water fraction and regional brain volumes exhibited age-dependent increases from childhood through adolescence, peaking at 15 years, followed by a decline in aged animals. Histological analyses revealed age-associated change...