In the article, “Resting State BOLD Variability of the Posterior Medial Temporal Lobe Correlates with Cognitive Performance in Older Adults with and without Risk for Cognitive Decline,” by Tyler J. Good, Joshua Villafuerte, Jennifer D. Ryan, Cheryl L. Grady, and Morgan D. Barense, which published online on March 19, 2020, Figure 3 B appeared incorrectly. The values for “3. Memory” …

Over half of all spinal cord injuries (SCIs) are cervical, which can lead to paralysis and respiratory compromise, causing significant morbidity and mortality. Effective treatments to restore breathing after severe upper cervical injury are lacking; thus, it is imperative to develop therapies to address this. Epidural stimulation has successfully restored motor function after SCI for stepping, standing, reaching, grasping, and postural control. We hypothesized that closed-loop stimulation triggered via healthy hemidiaphragm EMG activity has the potential to elicit functional neuroplasticity in spinal respiratory pathways after cervical SCI (cSCI). To test this, we delivered closed-loop, electrical, epidural stimulation (CLES) at the level of the phrenic motor nucleus (C4) for 3 d after C2 hemisection (C2HS) in freely behaving rats. A 2 × 2 Latin Square experimental design incorporated two treatments, C2HS injury and CLES therapy resulting in four groups of adult, female Sprague Dawley rats: C2HS + CLES ( n...

The neuropeptide oxytocin (Oxt) plays important roles in modulating social behaviors. Oxt receptor (Oxtr) is abundantly expressed in the brain and its relationship to socio-behavioral controls has been extensively studied using mouse brains. Several genetic tools to visualize and/or manipulate Oxtr-expressing cells, such as fluorescent reporters and Cre recombinase drivers, have been generated by ES-cell based gene targeting or bacterial artificial chromosome (BAC) transgenesis. However, these mouse lines displayed some differences in their Oxtr expression profiles probably because of the complex context and integrity of their genomic configurations in each line. Here, we apply our sophisticated genome-editing techniques to the Oxtr locus, systematically generating a series of knock-in mouse lines, in which its endogenous transcriptional regulations are intactly preserved and evaluate their expression profiles to ensure the reliability of our new tools. We employ the epitope tagging strategy, with which C-...

The dorsal raphe nucleus (DRN) contains the largest population of serotonin (5-HT) neurons in the central nervous system. 5-HT, synthesized via tryptophan hydroxylase 2 (Tph2), is a widely functioning neuromodulator implicated in fear learning. Here, we sought to investigate whether DRN 5-HT is necessary to reduce fear via negative prediction error (–PE). Using male and female TPH2-cre rats, DRNtph2+ cells were selectively deleted via cre-caspase (rAAV5-Flex-taCasp3-TEVp) in experiment 1. Rats then underwent fear discrimination during which three cues were associated with unique foot shock probabilities: safety p  = 0.00, uncertainty p  = 0.375, and danger p  = 1.00. Rats then received selective extinction to the uncertainty cue, a behavioral manipulation designed to probe –PE. Deleting DRNtph2+ cells had no impact on initial discrimination but slowed selective extinction. In experiment 2, we used a within-subjects optogenetic inhibition design to causally implicate DRNtph2+ cells in prediction error signa...

In the article, “Induction of Short-Term Sensitization by an Aversive Chemical Stimulus in Zebrafish Larvae,” by Adam C. Roberts, Joseph B. Alzagatiti, Duy T. Ly, Julia M. Chornak, Yuqi Ma, Asif Razee, Gohar Zavradyan, Umair Khan, Julia Lewis, Aishwarya Natarajan, Alisher Baibussinov, Jasmine Emtage, Meghna Komaranchath, Jared Richards, Michelle Hoang, Jason Alipio, Emma Laurent, Amit …

Stereoscopic vision enables the perception of depth. To study the brain mechanisms behind stereoscopic vision using noninvasive brain imaging (magnetic resonance brain imaging; MRI), scientists need to reproduce the independent views of the left and right eyes in the brain scanner using “dichoptic” displays. However, high-quality dichoptic displays are technically challenging and costly to implement in the MRI scanner. The novel miniature stereoscope system (“MRI stereoscope”) is an affordable and open-source tool that displays high-quality dichoptic images inside the MRI scanner. The MRI stereoscope takes advantage of commonly used display equipment, the MRI head coil, and a display screen. To validate the MRI stereoscope, binocular disparity stimuli were presented in a 3T MRI scanner while neural activation was recorded using functional MRI in six human participants. The comparison of large binocular disparities compared with disparities close to zero evoked strong responses across dorsal and ventral ext...

The aging brain undergoes structural changes even in very healthy individuals. Quantifying these changes could help disentangle pathologic changes from those associated with the normal human aging process. Using longitudinal magnetic resonance imaging (MRI) data from 227 carefully selected healthy human cohort with age ranging from 50 to 80 years old at baseline scan, we quantified age-related volumetric changes in the brain of healthy human older adults. Longitudinally, the rates of tissue loss in total gray matter (GM) and white matter (WM) were 2497.5 and 2579.8 mm3 per year, respectively. Across the whole brain, the rates of GM decline varied with regions in the frontal and parietal lobes having faster rates of decline, whereas some regions in the occipital and temporal lobes appeared relatively preserved. In contrast, cross-sectional changes were mainly observed in the temporal-occipital regions. Similar longitudinal atrophic changes were also observed in subcortical regions including thalamus, hippoc...

Hippocampal neural disinhibition, i.e., reduced GABAergic inhibition, is a key feature of schizophrenia pathophysiology. The hippocampus is an important part of the neural circuitry that controls fear conditioning and can also modulate prefrontal and striatal mechanisms, including dopamine signaling, which play a role in salience modulation. Consequently, hippocampal neural disinhibition may contribute to impairments in fear conditioning and salience modulation reported in schizophrenia. Therefore, we examined the effect of ventral hippocampus (VH) disinhibition in male rats on fear conditioning and salience modulation, as reflected by latent inhibition (LI), in a conditioned emotional response (CER) procedure. A flashing light was used as the conditioned stimulus (CS), and conditioned suppression was used to index conditioned fear. In experiment 1, VH disinhibition via infusion of the GABA-A receptor antagonist picrotoxin before CS pre-exposure and conditioning markedly reduced fear conditioning to both t...

Oxytocin (Oxt) controls reproductive physiology and various kinds of social behaviors, but the exact contribution of Oxt to different components of parental care still needs to be determined. Here, we illustrate the neuroanatomical relations of the parental nurturing-induced neuronal activation with magnocellular Oxt neurons and fibers in the medial preoptic area (MPOA), the brain region critical for parental and alloparental behaviors. We used genetically-targeted mouse lines for Oxt , Oxt receptor ( Oxtr ), vasopressin receptor 1a ( Avpr1a ), vasopressin receptor 1b ( Avpr1b ), and thyrotropin-releasing hormone ( Trh ) to systematically examine the role of Oxt-related signaling in pup-directed behaviors. The Oxtr - Avpr1a - Avpr1b triple knock-out (TKO), and Oxt - Trh - Avpr1a - Avpr1b quadruple KO (QKO) mice were grossly healthy and fertile, except for their complete deficiency in milk ejection and modest deficiency in parturition secondary to maternal loss of the Oxt or Oxtr gene. In our minimal stress...

The neurophysiological processes reflecting body illusions such as the rubber hand remain debated. Previous studies investigating the neural responses evoked by the illusion-inducing stimulation have provided diverging reports as to when these responses reflect the illusory state of the artificial limb becoming embodied. One reason for these diverging reports may be that different studies contrasted different experimental conditions to isolate potential correlates of the illusion, but individual contrasts may reflect multiple facets of the adopted experimental paradigm and not just the illusory state. To resolve these controversies, we recorded EEG responses in human participants and combined multivariate (cross-)classification with multiple Illusion and non-Illusion conditions. These conditions were designed to probe for markers of the illusory state that generalize across the spatial arrangements of limbs or the specific nature of the control object (a rubber hand or participant’s real hand), hence which...