Journal of Neuroscience最新文献

The multifactorial pathophysiology of acquired epilepsies lends itself to a multitargeting therapeutic approach. MicroRNAs (miRNA) are short noncoding RNAs that individually can negatively regulate dozens of protein-coding transcripts. Previously, we reported that central injection of antisense oligonucleotides targeting microRNA-134 (Ant-134) shortly after status epilepticus potently suppressed the development of recurrent spontaneous seizures in rodent models of temporal lobe epilepsy. The mechanism(s) of these antiseizure effects remain, however, incompletely understood. Here we show that intracerebroventricular microinjection of Ant-134 in male mice with preexisting epilepsy caused by intra-amygdala kainic acid-induced status epilepticus potently reduces the occurrence of spontaneous seizures. Recordings from ex vivo brain slices collected 2-4 d after Ant-134 injection in epileptic mice detected a number of electrophysiological phenotypic changes consistent with reduced excitability. Specifically, Ant-134 reduced action potential bursts after current injection in CA1 neurons and reduced excitatory postsynaptic current frequencies in CA1 neurons. Ant-134 also reduced general network excitability, including attenuating proexcitatory CA1 responses to Schaffer collateral stimulation in hippocampal slices from epileptic mice. Together, the present study demonstrates inhibiting miR-134 reduces single neuron and network hyperexcitability in mice and extends support for this approach to treat drug-resistant epilepsies.

The brain and spinal cord originate from a neural tube that is preceded by a flat structure known as the neural plate during early embryogenesis. In humans, failure of the neural plate to convert into a tube by the fourth week of pregnancy leads to neural tube defects (NTDs), birth defects with serious neurological consequences. The signaling mechanisms governing the process of neural tube morphogenesis are unclear. Here we show that in Xenopus laevis embryos, glutamate is released during neural plate folding in a Ca²⁺ and vesicular glutamate transporter-1 (VGluT1)-dependent manner. Vesicular release of glutamate elicits Ca²⁺ transients in neural plate cells that correlate with activation of Erk1/2. Knocking down or out VGluT1, globally or neural tissue-specifically, leads to NTDs and increased expression of Sox2, neural stem cell transcription factor, and neural plate cell proliferation. Exposure during early pregnancy to neuroactive drugs that disrupt these signaling mechanisms might increase the risk of NTDs in offspring.

During sleep, the human brain transitions to a "sentinel processing mode," enabling the continued processing of environmental stimuli despite the absence of consciousness. We employed advanced information-theoretic analyses, including mutual information (MI) and co-information (co-I), alongside event-related potential (ERP) and temporal generalization analyses (TGA), to characterize auditory prediction error processing across wakefulness and sleep. We hypothesized that a shared neural code would be present across sleep stages, with deeper sleep being associated with reduced information content and increased information redundancy. Twenty-nine participants (15 women) underwent an auditory "local-global" oddball paradigm during wakefulness and an 8 h sleep opportunity monitored via polysomnography. We focused on "local" mismatch responses to a deviating fifth tone after four standards. ERP analyses showed that prediction error processing continued throughout all sleep stages (N1-N3, REM). Mutual information analyses revealed a substantial reduction in encoded prediction error information particularly during N3 and REM, although ERP amplitudes increased with deeper NREM sleep. We also observed delayed information encoding during sleep, and co-information analyses showed neural dynamics became increasingly redundant with increasing sleep depth. TGA revealed a largely shared neural code between N2 and N3, though it differed between wakefulness and sleep. We demonstrate how the neural code of the "sentinel processing mode" changes from wake to light to deep sleep and REM, characterized by delayed processing, more redundant and less rich neural information in the human cortex as consciousness wanes. This altered stimulus processing reveals how neural information evolves with variations in consciousness across the night.

Rewards signal information in the environment that is valuable and thus useful to remember. Rewards benefit memory across development, but how reward-associated memories are represented in the brain has not been well characterized. Here we conducted pattern similarity analyses of fMRI data in male and female participants aged 8-25 to elucidate how neural representations in key memory-related brain areas are influenced by reward and how these relationships change across childhood and adolescence. We found that reward information was reflected in pattern similarity during encoding in the ventral temporal cortex and in changes in similarity from encoding to retrieval in anterior hippocampus (aHC). Strikingly, aHC reward-sensitive representations also varied with age such that adults' memory benefitted from stability of hippocampal representations, whereas younger participants' memory improvements were associated with greater drift in representations over time. Moreover, across all participants, reward-related univariate activation in the ventral tegmental area was associated with a greater tendency toward representational drift in aHC. Taken together, our findings demonstrate that reward modulates neural memory representations and that the representational patterns supporting reward-motivated memory shift with age.

The prefrontal cortex (PFC) and hippocampus (HPC) reportedly play crucial roles in the flexible use of stored information according to context. However, it remains unclear whether and how their neural representations differ during the context-guided retrieval. To solve this problem, we examined neural activity in the lateral PFC (lPFC, 470 neurons), medial PFC (mPFC, 322 neurons), and HPC (456 neurons) of three male macaques performing an item-location association memory task. The task required the animals to remember the location of a firstly presented item-cue relative to a background image that was later shown with a tilt as a context-cue. Population decoding analyses using all recorded neurons suggested that the lPFC and HPC (but not the mPFC) represented substantial task-related information. However, the represented contents differed between the two areas, both before and after the context-cue. Before the context-cue, the lPFC represented only the location retrieved from the item-cue, while the HPC also represented the item-cue itself. After the context-cue, the lPFC demonstrated a selective representation of the target-location regardless of the context-cue. In contrast, the HPC represented the three task-related pieces of information equivalently. These results suggest that the lPFC selectively represents goal-directed information at that moment among task-related information, while the HPC automatically represents a task event and its mnemonically linked information, implying complementary functional roles of the two brain regions as "regulator" and "supplier" in the context-guided memory process.

Neuronal oscillations are a ubiquitous feature of thalamocortical networks and can be dynamically modulated across processing states, enabling thalamocortical communication to flexibly adapt to varying environmental and behavioral demands. The lateral geniculate nucleus (LGN), like all thalamic nuclei, engages in reciprocal synaptic interactions with the cortex, relaying retinal information to and receiving feedback input from primary visual cortex (V1). While retinal excitation is the primary driver of LGN activity, retinal synapses represent a minority of the total synaptic input onto LGN neurons, allowing for both retinogeniculate and geniculocortical signals to be influenced by nonretinal sources. To gain a holistic view of network processing in the geniculocortical pathway, we performed simultaneous extracellular recordings from the LGN and V1 of behaving macaque monkeys (two male, four female), measuring local field potentials (LFPs) and spiking activity. These recordings revealed prominent beta-band oscillations coherent between the LGN and V1 that influenced spike timing in the LGN and were statistically consistent with a feedforward process from the LGN to V1. These thalamocortical oscillations were suppressed by visual stimulation, spatial attention, and behavioral arousal, strongly suggesting that these oscillations are not a feature of active visual processing. Instead, they appear analogous to occipital lobe, alpha oscillations recorded in humans and may represent a signature of signal suppression that occurs during periods of low engagement or active distractor suppression.

Episodic memory retrieval engages both sensory reinstatement and internally transformed representations. Due to modality-specific processing, auditory and visual memories may differ in their reliance on these mechanisms. We used functional magnetic resonance imaging and multivoxel pattern analyses to examine how 25 participants (12 males and 13 females) encoded and retrieved naturalistic sounds and videos. Both auditory and visual targets reinstated event-specific fine activation patterns in the association cortex during retrieval, and reinstatement strength correlated with subjective memory vividness. However, after removing encoding traces, auditory episodes showed a markedly larger reliance on internally transformed traces than visual episodes, quantified by "reinstatement-free" retrieval-retrieval similarity. Sensory reinstatement correlated more with the (detail-related) posterior hippocampus, while internal representations also correlated with the (gist-related) anterior hippocampus. Furthermore, temporal voice areas preserved gist-level (human vs nonhuman) information from encoding to retrieval, whereas fusiform face representations degraded. These findings reveal that auditory and visual memories share a common sensory reinstatement mechanism but differ in the neural mechanism that supports retrieval, with participants favoring gist over perceptual details during auditory memory retrieval.