Neurons in posterior parietal cortex (PPC) encode many aspects of the sensory world (e.g., scene structure), the posture of the body, and plans for action. For a downstream computation, however, only some of these dimensions are relevant; the rest are “nuisance variables”, because their influence on neural activity changes with sensory and behavioral context, potentially corrupting the read-out of relevant information. Here we show that a key postural variable for vision – eye position – is represented robustly in male macaque PPC across a range of contexts, even though the tuning of single neurons depended strongly on context. Contexts were defined by different stages of a visually guided reaching task, including ( i ) a visually sparse epoch; ( ii ) a visually rich epoch; ( iii ) a “go” epoch in which the reach was cued; and ( iv ) during the reach itself. Eye position was constant within trials but varied across trials in a 3 × 3 grid spanning 24° × 24°. Using demixed principal component analysis of neu...

The neural processes that enable healthy humans to orient attention to sudden visual events are poorly understood because they are tightly intertwined with purely sensory processes. Here we isolated visually guided orienting activity from sensory activity using event-related potentials (ERPs). By recording ERPs to a lateral stimulus and comparing waveforms obtained under conditions of attention and inattention, we identified an early positive deflection over the ipsilateral visual cortex that was associated with the covert orienting of visual attention to the stimulus. Across five experiments with male and female adults participants, this ipsilateral visual orienting activity (VOA) could be distinguished from purely sensory-evoked activity and from other top-down spatial attention effects. The VOA was linked with behavioral measures of orienting, being significantly larger when the stimulus was detected rapidly than when it was detected more slowly, and its presence was independent of saccadic eye movement...

The hippocampus is critical for rapid acquisition of many forms of memory, although the circuit-level mechanisms through which the hippocampus rapidly consolidates novel information are unknown. Here, activity of large ensembles of hippocampal neurons in adult male Long-Evans rats were monitored across a period of rapid spatial learning to assess how the network changes during the initial phases of memory formation and retrieval. In contrast to several reports, the hippocampal network did not display enhanced representation of the goal location via accumulation of place fields or elevated firing rates at the goal. Rather, population activity rates increased globally as a function of experience. These alterations in activity were mirrored in the power of the theta oscillation and in the quality of theta sequences, without preferential encoding of paths to the learned goal location. In contrast, during brief ‘offline’ pauses in movement representation of a novel goal location emerged rapidly in ripples, prec...

Retinal ganglion cells (RGCs) die after optic nerve trauma or in degenerative disease. However, acute changes in protein expression that may regulate RGC response to injury are not fully understood, and detailed methods to quantify new protein synthesis have not been tested. Here we develop and apply a new in vivo quantitative measure of newly synthesized proteins to examine changes occurring in the retina after optic nerve injury. Azidohomoalanine (AHA), a noncanonical amino acid, was injected intravitreally into the eyes of rodents of either sex with or without optic nerve injury. Isotope variants of biotin-alkyne were used for quantitative BONCAT (QBONCAT) mass spectrometry, allowing identification of protein synthesis and transport rate changes in over 1000 proteins at 1 or 5 days after optic nerve injury. In vitro screening showed several newly synthesized proteins regulate axon outgrowth in primary neurons in vitro . This novel approach to targeted quantification of newly synthesized proteins after i...

Ten eleven translocation (TET) proteins are crucial epigenetic regulators highly conserved in multicellular organisms. TETs’ enzymatic function in demethylating 5-methyl cytosine in DNA is required for proper development and TETs are frequently mutated in cancer. Recently, Drosophila melanogaster Tet (dTet) was shown to be highly expressed in developing fly brains and discovered to play an important role in brain and muscle development as well as fly behavior. Furthermore, dTet was shown to have different substrate specificity compared to mammals. However, the exact role dTet plays in glial cells and how ectopic TET expression in glial cells contributes to tumorigenesis and glioma is still not clear. Here, we report a novel role for dTet specifically in glial cell organization and number. We show that loss of dTet affects the organization of a specific glia population in the optic lobe, the “optic chiasm” glia. Additionally, we find irregularities in axon patterns in the ventral nerve cord (VNC) both, in t...

Spatial memory and reward processing are known to be disrupted in schizophrenia. Since the lateral septum (LS) may play an important role in the integration of location and reward, we examined the effect of maternal immune activation (MIA), a known schizophrenia risk factor, on spatial representation in the rat LS. In support of a previous study, we found that spatial location is represented as a phase code in the rostral LS of adult male rats, so that LS cell spiking shifts systematically against the phase of the hippocampal, theta-frequency, local field potential (LFP) as an animal moves along a track towards a reward (phase precession). Whereas shallow precession slopes were observed in control (CTL) group cells, they were steeper in the MIA animals, such that firing frequently precessed across several theta cycles as the animal moved along the length of the apparatus, with subsequent ambiguity in the phase representation of location. Furthermore, an analysis of the phase trajectories of the CTL group c...

Aversive responses to bright light (photoaversion) require signaling from the eye to the brain. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) encode absolute light intensity and are thought to provide the light signals for photoaversion. Consistent with this, neonatal mice exhibit photoaversion prior to the developmental onset of image vision, and melanopsin deletion abolishes photoaversion in neonates. It is not well understood how the population of ipRGCs, which constitutes multiple physiologically distinct types (denoted M1-M6 in mouse), encodes light stimuli to produce an aversive response. Here, we provide several lines of evidence that M1 ipRGCs that lack the Brn3b transcription factor drive photoaversion in neonatal mice. First, neonatal mice lacking TRPC6 and TRPC7 ion channels failed to turn away from bright light, while two photon Ca2+ imaging of their acutely isolated retinas revealed reduced photosensitivity in M1 ipRGCs, but not other ipRGC types. Second, m...

Steady-state visually evoked potentials (SSVEP) are widely used to index top-down cognitive processing in human electroencephalogram (EEG) studies. Typically, two stimuli flickering at different temporal frequencies (TFs) are presented, each producing a distinct response in the EEG at its flicker frequency. However, how SSVEP responses in EEG are modulated in the presence of a competing flickering stimulus just due to sensory interactions is not well understood. We have previously shown in local field potentials (LFP) recorded from awake monkeys that when two overlapping full screen gratings are counter-phased at different TFs, there is an asymmetric SSVEP response suppression, with greater suppression from lower TFs, which further depends on the relative orientations of the gratings (stronger suppression and asymmetry for parallel compared to orthogonal gratings). Here, we first confirmed these effects in both male and female human EEG recordings. Then, we mapped the response suppression of one stimulus (...

During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to CNS insults, positioning these cells to have profound impact on the function of nearby neurons. We and others recently showed that microglial attributes differ significantly across brain regions in young adult mice. However, the degree to which microglial properties vary during aging is largely unexplored. Here, we analyze and manipulate microglial aging within the basal ganglia, brain circuits that exhibit prominent regional microglial heterogeneity and where neurons are vulnerable to functional decline and neurodegenerative disease. In male and female mice, we demonstrate that ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) microglia exhibit unique and premature responses to aging, compared to cortex and nucleus accumbens (NAc) microglia. This is associated with localized VTA/SNc neuroinflammation that may compromise synaptic function...

The opioid crisis has contributed to a growing population of children exposed to opioids during fetal development; however, many of the long-term effects of opioid exposure on development are unknown. We previously demonstrated that opioids have deleterious effects on endocannabinoid plasticity at glutamate synapses in the dorsal striatum of adolescent rodents, but it is unclear if prenatal opioid exposure produces similar neuroadaptations. Using a mouse model of prenatal methadone exposure (PME), we performed proteomics, phosphoproteomics, and patch-clamp electrophysiology in the dorsolateral and dorsomedial striatum (DLS & DMS, respectively) to examine synaptic functioning in adolescent PME offspring. PME impacted the proteome and phosphoproteome in a region- and sex-dependent manner. Many proteins and phosphorylated proteins associated with glutamate transmission were differentially abundant in PME offspring which was associated with reduced glutamate release in the DLS and altered the rise time of exci...