Early studies in mouse neurodevelopment led to the discovery of the RE1 Silencing Transcription Factor (REST) and its role as a master repressor of neuronal gene expression. Recently, REST was reported to also repress neuronal genes in the human adult brain. These genes were found to be involved in pro-apoptotic pathways; and their repression, associated with increased REST levels during aging, were found to be neuroprotective and conserved across species. However, direct genome-wide REST binding profiles for REST in adult brain have not been identified for any species. Here, we apply this approach to mouse and human hippocampus. We find an expansion of REST binding sites in the human hippocampus that are lacking in both mouse hippocampus and other human non-neuronal cell types. The unique human REST binding sites are associated with genes involved in innate immunity processes and inflammation signaling which, on the basis of histology and recent public transcriptomic analyses, suggest that these new targe...

Understanding the bioenergetics of axon extension and maintenance has wide ranging implications for neurodevelopment and disease states. Glycolysis is a pathway consisting of 10 enzymes and separated into preparatory and payoff phases, the latter producing ATP. Using embryonic chicken sensory neurons, we report that glycolytic enzymes are found through the axon and the growth cone. Pharmacological inhibition of glycolysis in the presence of NGF impairs axon extension and growth cone dynamics within minutes without affecting axon maintenance. Experiments using microfluidic chambers show that the effect of inhibiting glycolysis on axon extension is local along distal axons and can be reversed by promoting mitochondrial respiration. Knockdown of GAPDH simplifies growth cone morphology and is rescued by shRNA-resistant GAPDH expression. Rescue of GAPDH using KillerRed fused to GAPDH followed by localized chromophore-assisted light inactivation of KillerRed-GAPDH in distal axons halts growth cone dynamics. Cons...

Paternal care plays a critical role in the development of brain and behaviors in offspring in monogamous species. However, the neurobiological mechanisms, especially the neuronal circuity, underlying paternal care is largely unknown. Using socially monogamous male mandarin voles ( Microtus mandarinus ) with high levels of paternal care, we found that paraventricular nucleus of the hypothalamus (PVN) to ventral tegmental area (VTA) or nucleus accumbens (NAc) oxytocin (OT) neurons are activated during paternal care. Chemogenetic activation/inhibition of the PVN OT projection to VTA promoted/decreased paternal care, respectively. Chemogenetic inhibition of the PVN to VTA OT pathway reduced dopamine (DA) release in the NAc of male mandarin voles during licking and grooming of pups as revealed by in vivo fiber photometry. Optogenetic activation/inhibition of the VTA to NAc DA pathway possibly enhanced/suppressed paternal behaviors, respectively. Furthermore, chemogenetic activation/inhibition of PVN to NAc OT c...

Over the past decades, numerous studies have linked cortical gamma oscillations (∼30–100 Hz) to neurocomputational mechanisms. Their functional relevance, however, is still passionately debated. Here, we asked whether endogenous gamma oscillations in the human brain can be entrained by a rhythmic photic drive >50 Hz. Such a noninvasive modulation of endogenous brain rhythms would allow conclusions about their causal involvement in neurocognition. To this end, we systematically investigated oscillatory responses to a rapid sinusoidal flicker in the absence and presence of endogenous gamma oscillations using magnetoencephalography (MEG) in combination with a high-frequency projector. The photic drive produced a robust response over visual cortex to stimulation frequencies of up to 80 Hz. Strong, endogenous gamma oscillations were induced using moving grating stimuli as repeatedly done in previous research. When superimposing the flicker and the gratings, there was no evidence for phase or frequency entrainme...

During music listening, humans routinely acquire the regularities of the acoustic sequences and use them to anticipate and interpret the ongoing melody. Specifically, in line with this predictive framework, it is thought that brain responses during such listening reflect a comparison between the bottom-up sensory responses and top-down prediction signals generated by an internal model that embodies the music exposure and expectations of the listener. To attain a clear view of these predictive responses, previous work has eliminated the sensory inputs by inserting “artificial” silences (or sound omissions) that leave behind only the corresponding predictions of the thwarted expectations. Here we demonstrate a new alternate approach in which we decode the predictive EEG responses to the silent intervals that are naturally interspersed within the music. We did this as participants (experiment 1: twenty participants, ten female; experiment 2: twenty-one participants, 6 female) both listened or imagined Bach pi...

Oligodendrocytes generate myelin sheaths vital for the formation, health and function of the central nervous system (CNS). Myelin sheath length is a key property that determines axonal conduction velocity and is known to be variable across the CNS. Myelin sheath length can be modified by neuronal activity, suggesting that dynamic regulation of sheath length might contribute to the functional plasticity of neural circuits. Although the mechanisms that establish and refine myelin sheath length are important determinants of brain function, our understanding of these remains limited. In recent years, the membranes of myelin sheaths have been increasingly recognised to contain ion channels and transporters that are associated with specific important oligodendrocyte functions, including metabolic support of axons and the regulation of ion homeostasis, but none have been shown to influence sheath architecture. In this study, we determined that hyperpolarisation-activated, cyclic nucleotide-gated (HCN) channels, t...

Musical imagery is the voluntary internal hearing of music in the mind without the need for physical action or external stimulation. Numerous studies have already revealed brain areas activated during imagery. However, it remains unclear to what extent imagined music responses preserve the detailed temporal dynamics of the acoustic stimulus envelope and, crucially, whether melodic expectations play any role in modulating responses to imagined music, as they prominently do during listening. These modulations are important as they reflect aspects of the human musical experience, such as its acquisition, engagement, and enjoyment. This study explored the nature of these modulations in imagined music based on EEG recordings from 21 professional musicians (6 females and 15 males). Regression analyses were conducted to demonstrate that imagined neural signals can be predicted accurately, similarly to the listening task, and were sufficiently robust to allow for accurate identification of the imagined musical pie...

How does the brain anticipate information in language? When people perceive speech, low-frequency (< 10 Hz) activity in the brain synchronizes with bursts of sound and visual motion. This phenomenon, called cortical stimulus-tracking, is thought to be one way that the brain predicts the timing of upcoming words, phrases, and syllables. In this study, we test whether stimulus-tracking depends on domain-general expertise or on language-specific prediction mechanisms. We go on to examine how the effects of expertise differ between frontal and sensory cortex. We recorded electroencephalography (EEG) from human participants who were experts in either sign language or ballet, and we compared stimulus-tracking between groups while participants watched videos of sign language or ballet. We measured stimulus-tracking by computing coherence between EEG recordings and visual motion in the videos. Results showed that stimulus-tracking depends on domain-general expertise, and not on language-specific prediction mechani...