In mammalian cortex, feedforward excitatory connections recruit feedforward inhibition. This is often carried by parvalbumin (PV+) interneurons, which may densely connect to local pyramidal (Pyr) neurons. Whether this inhibition affects all local excitatory cells indiscriminately or is targeted to specific subnetworks is unknown. Here, we test how feedforward inhibition is recruited by using 2-channel circuit mapping to excite cortical and thalamic inputs to PV+ interneurons and Pyr neurons to mouse motor cortex. Single Pyr and PV+ neurons receive input from both cortex and thalamus. Connected pairs of PV+ interneurons and excitatory Pyr neurons receive correlated cortical and thalamic inputs. While PV+ interneurons are more likely to form local connections to Pyr neurons, Pyr neurons are much more likely to form reciprocal connections with PV+ interneurons that inhibit them. This suggests that Pyr and PV ensembles may be organized based on their local and long-range connections, an organization that suppo...

Oligodendrogenesis is the process by which new oligodendrocytes are produced in the central nervous system. Oligodendrocytes form myelin, which has a vital role in neural signal transmission and integration. Here we tested mice with reduced adult oligodendrogenesis in the Morris watermaze, a test of spatial learning. These mice were found to have impaired long-term (28-day) spatial memory. However, when 7,8-dihydroxyflavone (7,8-DHF) was administered immediately after each training session, their long-term spatial memory impairment was rescued. An increase in the number of newly formed oligodendrocytes in the corpus callosum was also observed. 7,8-DHF has previously been shown to improve spatial memory in animal models of Alzheimer’s diseases, post-traumatic stress disorder (PTSD), Wolfran and Down syndrome, as well as in normal aging. Understanding the underlying mechanisms of this drug on spatial memory is therefore helpful in assessing it for clinical relevance and development. Significance Statement ...

Exercise may prevent or delay aging-related memory loss and neurodegeneration. In rodents, running increases the number of adult-born neurons in the dentate gyrus (DG) of the hippocampus, in association with improved synaptic plasticity and memory function. However, it is unclear if adult-born neurons remain fully integrated into the hippocampal network during aging and whether long-term running affects their connectivity. To address this issue we labeled proliferating DG neural progenitor cells with retrovirus expressing the avian TVA receptor in 2-month-old sedentary and running male C57Bl/6 mice. More than six months later, we injected EnvA-pseudotyped rabies virus into the DG as a monosynaptic retrograde tracer, to selectively infect TVA expressing ‘old’ new neurons. We identified and quantified the direct afferent inputs to the adult-born neurons within the hippocampus and (sub)cortical areas. Here we show that long-term running substantially modifies the network of the neurons generated in young adul...

Therapeutic hypothermia is well-established as a standard treatment for infants with hypoxic-ischemic encephalopathy but it is only partially effective. The potential for combination treatments to augment hypothermic neuroprotection has major relevance. Our aim was to assess the effects of treating newborn rats following hypoxic-ischemic (HI) injury with cannabidiol (CBD) at 0.1 or 1 mg/kg i.p., in normothermic (37.5°C) and hypothermic (32.0°C) conditions, from 7 (neonatal phase) to 37 days old (juvenile phase). Placebo or CBD were administered at 0.5, 24 and 48 h after HI injury. Two sensorimotor (rotarod and cylinder rearing), and two cognitive (novel object recognition and T-maze) tests were conducted 30 days after HI. The extent of brain damage was determined by magnetic resonance imaging, histological evaluation, magnetic resonance spectroscopy, amplitude-integrated electroencephalography and Western blotting. At 37 days, the HI insult produced impairments in all neurobehavioral score (cognitive and s...

Reverberation is ubiquitous in everyday acoustic environments. It degrades both binaural cues and the envelope modulations of sounds and thus can impair speech perception. Still, both humans and animals can accurately perceive reverberant stimuli in most everyday settings. Previous neurophysiological and perceptual studies have suggested the existence of neural mechanisms that partially compensate for the effects of reverberation. However, these studies were limited by their use of either highly simplified stimuli or rudimentary reverberation simulations. To further characterize how reverberant stimuli are processed by the auditory system, we recorded single-unit (SU) and multiunit (MU) activity from the inferior colliculus (IC) of unanesthetized rabbits in response to natural speech utterances presented with no reverberation (“dry”) and in various degrees of simulated reverberation (direct-to-reverberant energy ratios (DRRs) ranging from 9.4 to –8.2 dB). Linear stimulus reconstruction techniques (Mesgara...

The parabrachial complex (PB) is critically involved in aversive processes, and chronic pain is associated with amplified activity of PB neurons in rodent models of neuropathic pain. Here we demonstrate that catecholaminergic input from the caudal nucleus of the solitary tract (cNTScat)—a stress responsive region that integrates intero- and exteroceptive signals—causes amplification of PB activity and their sensory afferents. We used a virally mediated expression of a norepinephrine (NE) sensor, NE2h, fiber photometry, and extracellular recordings in anesthetized mice to show that noxious mechanical and thermal stimuli activate cNTS neurons. These stimuli also produce prolonged NE transients in PB that far outlast the noxious stimuli. Similar NE transients can be evoked by focal electrical stimulation of cNTS, a region that contains the noradrenergic A2 cell group that projects densely upon PB. In vitro , optical stimulation of cNTScat terminals depolarized PB neurons and caused a prolonged increase the fr...

SYNGAP1 haploinsufficiency in humans causes intellectual disability. SYNGAP1 is highly expressed in cortical excitatory neurons and, reducing its expression in mice accelerates the maturation of excitatory synapses during sensitive developmental periods, restricts the critical period window for plasticity, and impairs cognition. However, its specific role in interneurons remains largely undetermined. In this study, we investigated the effects of conditional Syngap1 disruption in medial ganglionic eminence (MGE)-derived interneurons on hippocampal interneuron firing properties and excitatory synaptic inputs, as well as on pyramidal cell synaptic inhibition and synaptic integration. We show that conditional Syngap1 disruption in MGE-derived interneurons results in cell-specific impairment of firing properties of hippocampal Nkx2.1 fast-spiking interneurons, with enhancement of their AMPAR-mediated excitatory synaptic inputs but compromised short-term plasticity. In contrast, regular-spiking Nkx2.1 interneu...

Taste cells are maintained by continuous turnover throughout a lifetime, yet the mechanisms of taste cell differentiation, and how taste sensations remain constant despite this continuous turnover, remain poorly understood. Here, we report that a transcription factor Etv1 (also known as Er81) is involved in the differentiation of taste cells responsible for the preference for sweet, umami, and salty tastes. Molecular analyses revealed that Etv1 is expressed by a subset of taste cells that depend on Skn-1a (also known as Pou2f3) for their generation and express T1R genes (responsible for sweet and umami tastes) or Scnn1a (responsible for amiloride-sensitive salty taste). Etv1CreERT2/CreERT2 mice express Etv1 isoform(s) but not Etv1 in putative proprioceptive neurons as comparable to wild-type mice, yet lack expression of Etv1 or an isoform in taste cells. These Etv1CreERT2/CreERT2 mice have the same population of Skn-1a-dependent cells in taste buds as wild-type mice but have altered gene expression in tast...

Traditional human electroencephalography experiments that study visuomotor processing use controlled laboratory conditions with limited ecological validity. In the real world, the brain integrates complex, dynamic, multimodal visuomotor cues to guide the execution of movement. The parietal and occipital cortices are especially important in the online control of goal-directed actions. Table tennis is a whole-body, responsive activity requiring rapid visuomotor integration that presents a myriad of unanswered neurocognitive questions about brain function during real world movement. The aim of this study was to quantify the electrocortical dynamics of the parieto-occipital cortices while playing a sport with high-density electroencephalography. We included analysis of power spectral densities, event-related spectral perturbations, intertrial phase coherences, event-related potentials, and event-related phase coherences of parieto-occipital source-localized clusters while participants played table tennis with ...

Intracortical microstimulation (ICMS) is commonly used in many experimental and clinical paradigms; however, its effects on the activation of neurons are still not completely understood. To document the responses of cortical neurons in awake non-human primates to stimulation, we recorded single-unit activity while delivering single-pulse stimulation via Utah arrays implanted in primary motor cortex of three macaque monkeys. Stimuli between 5-50 μA delivered to single channels reliably evoked spikes in neurons recorded throughout the array with delays of up to 12 milliseconds. ICMS pulses also induced a period of inhibition lasting up to 150 ms that typically followed the initial excitatory response. Higher current amplitudes led to a greater probability of evoking a spike and extended the duration of inhibition. The likelihood of evoking a spike in a neuron was dependent on the spontaneous firing rate as well as the delay between its most recent spike time and stimulus onset. Tonic repetitive stimulation b...