When listening to continuous speech, the human brain can track features of the presented speech signal. It has been shown that neural tracking of acoustic features is a prerequisite for speech understanding and can predict speech understanding in controlled circumstances. However, the brain also tracks linguistic features of speech, which may be more directly related to speech understanding. We investigated acoustic and linguistic speech processing as a function of varying speech understanding by manipulating the speech rate. In this paradigm, acoustic and linguistic speech processing is affected simultaneously but in opposite directions: When the speech rate increases, more acoustic information per second is present. In contrast, the tracking of linguistic information becomes more challenging when speech is less intelligible at higher speech rates. We measured the EEG of 18 participants (4 male) who listened to speech at various speech rates. As expected and confirmed by the behavioral results, speech und...

Traumatic brain injury (TBI) triggers a plethora of inflammatory events in the brain that aggravate secondary injury and impede tissue repair. Resident microglia (Mi) and blood-borne infiltrating macrophages (MΦ) are major players of inflammatory responses in the post-TBI brain and possess high functional heterogeneity. However, the plasticity of these cells has yet to be exploited to develop therapies that can mitigate brain inflammation and improve the outcome after TBI. This study investigated the transcription factor STAT1 as a key determinant of proinflammatory Mi/MΦ responses and aimed to develop STAT1 as a novel therapeutic target for TBI using a controlled cortical impact model of TBI on adult male mice. TBI induced robust upregulation of STAT1 in the brain at the subacute injury stage, which occurred primarily in Mi/MΦ. Intraperitoneal administration of fludarabine, a selective STAT1 inhibitor, markedly alleviated proinflammatory Mi/MΦ responses and brain inflammation burden after TBI. Such phenot...

Yongfang Zhao, Cheng Ma, Caixia Chen, Sicheng Li, Yangfan Wang, et al. (see pages [7466–7481][1]) After traumatic brain injury, microglia become activated and the blood–brain barrier ruptures, allowing peripheral macrophages to enter the brain. Both microglia and macrophages assume a range of

In the medical field, the implementation of Milestones by the Accreditation Council for Graduate Medical Education (ACGME) has provided a common understanding among clinical and academic supervisors and trainees related to the development of core competencies during graduate medical training. These Milestones help establish developmental trajectories and aspirational goals for the trainee. Unfortunately, training in graduate and postgraduate neuroscience lacks a standardized developmental progression of competencies or outcomes expected of trainees. Without such standardizations, it may be difficult for both the mentor and trainee to identify levels of improvement, which may impact the trainee's future success. Here, we discuss the value of developing a nonexhaustive framework that may be used to evaluate trainees with the expectation that it will provide a template to help with the development of future neuroscientists.

The mediodorsal thalamus is a multimodal region involved in a variety of cognitive behaviors, including olfactory attention, odor discrimination, and the hedonic perception of flavors. Although the mediodorsal thalamus forms connections with principal regions of the olfactory and gustatory networks, its role in processing olfactory and gustatory signals originating from the mouth remains unclear. Here, we recorded single-unit activity in the mediodorsal thalamus of behaving female rats during the intraoral delivery of individual odors, individual tastes, and odor-taste mixtures. Our results are the first to demonstrate that neurons in the mediodorsal thalamus dynamically encode chemosensory signals originating from the mouth. This chemoselective population is broadly tuned, exhibits excited and suppressed responses, and responds to odor-taste mixtures differently than an odor or taste alone. Furthermore, a subset of chemoselective neurons encodes the palatability-related features of tastes and may represen...

Temporal lobe epilepsy is common, but mechanisms of seizure initiation are unclear. We evaluated seizure initiation in female and male rats that had been systemically treated with pilocarpine, a widely used model of temporal lobe epilepsy. Local field potential (LFP) recordings from many brain regions revealed variable sites of earliest recorded seizure activity, but mostly the ventral hippocampal formation. To test whether inactivation of the ventral hippocampal formation would reduce seizures, mini-osmotic pumps were used to continually and focally deliver TTX. High doses of TTX infused unilaterally into the ventral hippocampal formation blocked seizures reversibly but also reduced LFP amplitudes in remote brain regions, indicating distant effects. A lower dose did not reduce LFP amplitudes in remote brain regions but did not reduce seizures when infused unilaterally. Instead, seizures tended to initiate in the contralateral ventral hippocampal formation. Bilateral infusion of the lower dose into the ven...

Interstitial collateral branching of axons is a critical component in the development of functional neural circuits. Axon collateral branches are established through a series of cellular processes initiated by the development of a specialized, focal F-actin network in axons. The formation, maintenance and remodeling of this F-actin patch is critical for the initiation of axonal protrusions that are subsequently consolidated to form a collateral branch. However, the mechanisms regulating F-actin patch dynamics are poorly understood. Fmn2 is a formin family member implicated in multiple neurodevelopmental disorders. We find that Fmn2 regulates the initiation of axon collateral protrusions in chick spinal neurons and in zebrafish motor neurons. Fmn2 localizes to the protrusion-initiating axonal F-actin patches and regulates the lifetime and size of these F-actin networks. The F-actin nucleation activity of Fmn2 is necessary for F-actin patch stability but not for initiating patch formation. We show that Fmn2 ...

Despite increased prevalence of maternal cannabis use, little is understood regarding potential long-term effects of prenatal cannabis exposure (PCE) on neurodevelopmental outcomes. While neurodevelopmental cannabis exposure increases the risk of developing affective/mood disorders in adulthood, the precise neuropathophysiological mechanisms in male and female offspring are largely unknown. Given the interconnectivity of the endocannabinoid system and the brain's fatty acid pathways, we hypothesized that prenatal exposure to Δ9-tetrahydrocannabinol (THC) may dysregulate fetal neurodevelopment through alterations of fatty-acid dependent synaptic and neuronal function in the mesolimbic system. To investigate this, pregnant Wistar rats were exposed to vehicle or THC (3mg/kg) from gestational day (GD) 7 until GD22. Anxiety-like, depressive-like, and reward-seeking behaviour, electrophysiology, and molecular assays were performed on adult male/female offspring. Imaging of fatty acids using matrix-assisted laser...

While recent studies have revealed an involvement of hippocampal interneurons in learning the association among time-separated events, its underlying cellular mechanisms remained not fully clarified. Here, we combined multi-channel recording and optogenetics to elucidate how the hippocampal parvalbumin-expressing interneurons (PV-IN) support associative learning. To address this issue, we trained the mice (box sexes) to learn hippocampus-dependent trace eyeblink conditioning (tEBC) where they associated a light flash conditioned stimulus (CS) with a corneal airpuff unconditioned stimuli (US) separated by a 250-ms time interval. We found that the hippocampal PV-INs exhibited learning-associated sustained activity at the early stage of tEBC acquisition. Moreover, the PV-IN sustained activity was positively correlated with the occurrence of conditioned eyeblink responses at the early learning stage. Suppression of the PV-IN sustained activity impaired the acquisition of tEBC, whereas the PV-IN activity suppre...