Shingo Nakazawa, Yumiko Yoshimura, Masahiro Takagi, Hidenobu Mizuno, and Takuji Iwasato (see pages [7637–7650][1]) Patterned spontaneous activity is required for proper formation of sensory maps in developing sensory pathways. In the developing somatosensory system of rodents, waves of

γ-frequency oscillations (30-120 Hz) in cortical networks influence neuronal encoding and information transfer, and are disrupted in multiple brain disorders. While synaptic inhibition is important for synchronization across the γ-frequency range, the role of distinct interneuronal subtypes in slow (<60 Hz) and fast γ states remains unclear. Here, we used optogenetics to examine the involvement of parvalbumin-expressing (PV+) and somatostatin-expressing (SST+) interneurons in γ oscillations in the mouse hippocampal CA3 ex vivo , using animals of either sex. Disrupting either PV+ or SST+ interneuron activity, via either photoinhibition or photoexcitation, led to a decrease in the power of cholinergically induced slow γ oscillations. Furthermore, photoexcitation of SST+ interneurons induced fast γ oscillations, which depended on both synaptic excitation and inhibition. Our findings support a critical role for both PV+ and SST+ interneurons in slow hippocampal γ oscillations, and further suggest that intense ...

Accumulating evidence suggests that forgetting is not necessarily a passive process but that we can, to some extent, actively control what we remember and what we forget. Although this intentional control of memory has potentially far-reaching implications, the factors that influence our capacity to intentionally control our memory are largely unknown. Here, we tested whether acute stress may disrupt the intentional control of memory and, if so, through which neural mechanism. We exposed healthy men and women to a stress ( n = 27) or control ( n = 26) procedure before they aimed repeatedly to retrieve some previously learned cue-target pairs and to actively suppress others. While control participants showed reduced memory for suppressed compared with baseline pairs in a subsequent memory test, this suppression-induced forgetting was completely abolished after stress. Using magnetoencephalography (MEG), we show that the reduced ability to suppress memories after stress is associated with altered theta activ...

Spatially-organized spontaneous activity is a characteristic feature of developing mammalian sensory systems. However, the transitions of spontaneous-activity spatial organization during development and related mechanisms remain largely unknown. We reported previously that layer 4 (L4) glutamatergic neurons in the mouse barrel cortex exhibit spontaneous activity with a patchwork-type pattern at postnatal day (P)5, which is during barrel formation. In the current work, we revealed that spontaneous activity in mouse barrel-cortex L4 glutamatergic neurons exhibits at least three phases during the first two weeks of postnatal development. Phase I activity has a patchwork-type pattern and is observed not only at P5, but also P1, before barrel formation. Phase II is found at P9, by which time barrel formation is completed, and exhibits broadly synchronized activity across barrel borders. Phase III emerges around P11 when L4-neuron activity is desynchronized. The Phase I activity, but not Phase II or III activity...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motoneurons (MNs) in a motor-unit (MU)-dependent manner. Glial dysfunction contributes to numerous aspects of the disease. At the neuromuscular junction (NMJ), early alterations in perisynaptic Schwann cell (PSC), glial cells at this synapse, may impact their ability to regulate NMJ stability and repair. Indeed, muscarinic receptors (mAChRs) regulate the repair phenotype of PSCs and are overactivated at disease-resistant NMJs [soleus muscle (SOL)] in SOD1G37R mice. However, it remains unknown whether this is the case at disease-vulnerable NMJs and whether it translates into an impairment of PSC-dependent repair mechanisms. We used SOL and sternomastoid (STM) muscles from SOD1G37R mice and performed Ca2+-imaging to monitor PSC activity and used immunohistochemistry to analyze their repair and phagocytic properties. We show that PSC mAChR-dependent activity was transiently increased at disease-vulnerable NMJs (STM muscle). Fur...

Task episodes consist of sequences of steps that are performed to achieve a goal. We used fMRI to examine neural representation of task identity, component items, and sequential position, focusing on two major cortical systems—the multiple-demand (MD) and default mode networks (DMN). Human participants (20 males, 22 females) learned six tasks each consisting of four steps. Inside the scanner, participants were cued which task to perform and then sequentially identified the target item of each step in the correct order. Univariate time course analyses indicated that intra-episode progress was tracked by a tonically increasing global response, plus an increasing phasic step response specific to MD regions. Inter-episode boundaries evoked a widespread response at episode onset, plus a marked offset response specific to DMN regions. Representational similarity analysis (RSA) was used to examine representation of task identity and component steps. Both networks represented the content and position of individual...

Excessive activation of mammalian target of rapamycin (mTOR) signaling is epileptogenic in genetic epilepsy. However, the exact role of microglial mTOR in acquired epilepsy remains to be clarified. In the present study, we found that mTOR is strongly activated in microglia following excitatory injury elicited by status epilepticus. To determine the role of microglial mTOR signaling in excitatory injury and epileptogenesis, we generated mice with restrictive deletion of mTOR in microglia. Both male and female mice were used in the present study. We found that mTOR-deficient microglia lost their typical proliferative and inflammatory responses to excitatory injury, whereas the proliferation of astrocytes was preserved. In addition, mTOR-deficient microglia did not effectively engulf injured/dying neurons. More importantly, microglial mTOR-deficient mice displayed increased neuronal loss and developed more severe spontaneous seizures. These findings suggest that microglial mTOR plays a protective role in miti...

Accumulating evidence has established a firm role for synaptic plasticity in the pathogenesis of neuropathic pain. Recent advances have highlighted the importance of dendritic spine remodeling in driving synaptic plasticity within the CNS. Identifying the molecular players underlying neuropathic pain induced structural and functional maladaptation is therefore critical to understanding its pathophysiology. This process of dynamic reorganization happens in unique phases that have diverse pathologic underpinnings in the initiation and maintenance of neuropathic pain. Recent evidence suggests that pharmacological targeting of specific proteins during distinct phases of neuropathic pain development produces enhanced antinociception. These findings outline a potential new paradigm for targeted treatment and the development of novel therapies for neuropathic pain. We present a concise review of the role of dendritic spines in neuropathic pain and outline the potential for modulation of spine dynamics by targetin...

Identifying and responding to threats is crucial for survival. Accordingly, the nervous systems of organisms as simple as sea slugs have evolved to support the formation of associations between noxious events (unconditioned stimuli [US]) and cues that predict them (conditioned stimuli [CS]): a

Injury induces synaptic, circuit, and systems reorganization. After unilateral amputation or stroke, this functional loss disrupts the interhemispheric interaction between intact and deprived somatomotor cortices to recruit deprived cortex in response to intact limb stimulation. This recruitment has been implicated in enhanced intact sensory function. In other patients, maladaptive consequences such as phantom limb pain can occur. We used unilateral whisker denervation in male and female mice to detect circuitry alterations underlying interhemispheric cortical reorganization. Enhanced synaptic strength from the intact cortex via the corpus callosum (CC) onto deep neurons in deprived primary somatosensory barrel cortex (S1BC) has previously been detected. It was hypothesized that specificity in this plasticity may depend on to which area these neurons projected. Increased connectivity to somatomotor areas such as contralateral S1BC, primary motor cortex (M1) and secondary somatosensory cortex (S2) may under...