Memory often combines information from different sensory modalities. Animal studies show that synchronized neuronal activity in the theta band (4–8 Hz) binds multimodal associations. Studies with human participants have likewise established that theta-phase synchronization augments the formation of declarative video–tone pair memories. Another form of associative learning, classical fear conditioning, models nondeclarative, emotional memory with distinct neuronal mechanisms. Typical fear-conditioning tasks pair a conditioned stimulus (CS) in one modality with an aversive unconditioned stimulus (US) in another. The present study examines the effects of CS–US synchronization in the theta band on fear memory formation in humans. In a fear generalization procedure, we paired one of five visual gratings of varying orientation (CS) with an aversive auditory US. We modulated the luminance of the CS and the volume of the US at a rate of 4 Hz. To manipulate the synchrony between visual and auditory input during fea...

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...

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...

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...

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...

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 …

The arcuate nucleus (ArcN) is an integrative hub for the regulation of energy balance, reproduction, and arterial pressure (AP), all of which are influenced by Angiotensin II (AngII); however, the cellular mechanisms and downstream neurocircuitry are unclear. Here, we show that ArcN AngII increases AP in female rats via two phases, both of which are mediated via activation of AngII type 1 receptors (AT1aRs): initial vasopressin-induced vasoconstriction, followed by slowly developing increases in sympathetic nerve activity (SNA) and heart rate (HR). In male rats, ArcN AngII evoked a similarly slow increase in SNA, but the initial pressor response was variable. In females, the effects of ArcN AngII varied during the estrous cycle, with significant increases in SNA, HR, and AP occurring during diestrus and estrus, but only increased AP during proestrus. Pregnancy markedly increased the expression of AT1aR in the ArcN with parallel substantial AngII-induced increases in SNA and MAP. In both sexes, the sympatho...

Insight into the cellular and circuit mechanisms underlying development of temporal lobe epilepsy (TLE) will provide a foundation for improved therapies. We studied a model in which an episode of prolonged seizures is followed by recovery lasting two weeks before emergence of spontaneous recurrent seizures. We focused on the interval between the prolonged seizures and the late onset recurrent seizures. We investigated the hippocampal mossy fiber CA3 pyramidal cell microcircuit in models spanning in vitro , in vivo , and ex vivo preparations. Expression of channelrhodopsin-2 in the dentate granule cells of DGC ChR mice enabled the selective activation of mossy fiber axons. In vivo studies revealed marked potentiation of mossy fiber evoked field potentials in hippocampal CA3 beginning within hours following seizures, a potentiation which persisted at least 7 d. Stimulation of mossy fibers in hippocampal slices in vitro using patterns of activity mimicking seizures induced LTP not only of the monosynaptic EPS...

The superior parietal lobule (SPL) integrates somatosensory, motor, and visual signals to dynamically control arm movements. During reaching, visual and gaze signals are used to guide the hand to the desired target location, while proprioceptive signals allow to correct arm trajectory, and keep the limb in the final position at the end of the movement. Three SPL areas are particularly involved in this process: V6A, PEc, PE. Here, we evaluated the influence of eye and arm position on single neuron activity of these areas during the holding period at the end of arm reaching movements, when the arm is motionless and gaze and hand positions are aligned. Two male macaques ( Macaca fascicularis ) performed a foveal reaching task while single unit activity was recorded from areas V6A, PEc, and PE. We found that at the end of reaching movements the neurons of all these areas were modulated by both eye position and static position of the arm. V6A and PEc showed a prevalent combination of gaze and proprioceptive inp...