Axons navigate through the embryo to construct a functional nervous system. A missing part of the axon navigation puzzle is how a single axon traverses distinct anatomic choice points through its navigation. The dorsal root ganglia (DRG) neurons experience such choice points. First, they navigate to the dorsal root entry zone (DREZ), then halt navigation in the peripheral nervous system to invade the spinal cord, and then reinitiate navigation inside the CNS. Here, we used time-lapse super-resolution imaging in zebrafish DRG pioneer neurons to investigate how embryonic axons control their cytoskeleton to navigate to and invade at the correct anatomic position. We found that invadopodia components form in the growth cone even during filopodia-based navigation, but only stabilize when the axon is at the spinal cord entry location. Further, we show that intermediate levels of DCC and cAMP, as well as Rac1 activation, subsequently engage an axon invasion brake. Our results indicate that actin-based invadopodia...

Eukaryotic cells maintain proteostasis through mechanisms that require cytoplasmic and mitochondrial translation. Genetic defects affecting cytoplasmic translation perturb synapse development, neurotransmission, and are causative of neurodevelopmental disorders, such as Fragile X syndrome. In contrast, there is little indication that mitochondrial proteostasis, either in the form of mitochondrial protein translation and/or degradation, is required for synapse development and function. Here we focus on two genes deleted in a recurrent copy number variation causing neurodevelopmental disorders, the 22q11.2 microdeletion syndrome. We demonstrate that SLC25A1 and MRPL40, two genes present in the microdeleted segment and whose products localize to mitochondria, interact and are necessary for mitochondrial ribosomal integrity and proteostasis. Our Drosophila studies show that mitochondrial ribosome function is necessary for synapse neurodevelopment, function, and behavior. We propose that mitochondrial proteosta...

A long-standing debate centers on whether the specialized skills acquired by music experts transfer to other cognitive domains. Musical training is a multisensory experience, and long-term practice has been found to be associated with neuroanatomic and neurofunctional changes ([Criscuolo et al.,

An indispensable feature of episodic memory is our ability to temporally piece together different elements of an experience into a coherent memory. Hippocampal time cells—neurons that represent temporal information—may play a critical role in this process. Although these cells have been repeatedly found in rodents, it is still unclear to what extent similar temporal selectivity exists in the human hippocampus. Here, we show that temporal context modulates the firing activity of human hippocampal neurons during structured temporal experiences. We recorded neuronal activity in the human brain while patients of either sex learned predictable sequences of pictures. We report that human time cells fire at successive moments in this task. Furthermore, time cells also signaled inherently changing temporal contexts during empty 10 s gap periods between trials while participants waited for the task to resume. Finally, population activity allowed for decoding temporal epoch identity, both during sequence learning an...

The human brain extracts statistical regularities embedded in real-world scenes to sift through the complexity stemming from changing dynamics and entwined uncertainty along multiple perceptual dimensions (e.g., pitch, timbre, location). While there is evidence that sensory dynamics along different auditory dimensions are tracked independently by separate cortical networks, how these statistics are integrated to give rise to unified objects remains unknown, particularly in dynamic scenes that lack conspicuous coupling between features. Using tone sequences with stochastic regularities along spectral and spatial dimensions, this study examines behavioral and electrophysiological responses from human listeners (male and female) to changing statistics in auditory sequences and uses a computational model of predictive Bayesian inference to formulate multiple hypotheses for statistical integration across features. Neural responses reveal multiplexed brain responses reflecting both local statistics along individ...

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...

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...