Hiroki Sugihara

miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity

Using quantitative analyses, we identified microRNAs (miRNAs) that were abundantly expressed in visual cortex and that responded to dark rearing and/or monocular deprivation. The most substantially altered miRNA, miR-132, was rapidly upregulated after eye opening and was delayed by dark rearing. In vivo inhibition of miR-132 in mice prevented ocular dominance plasticity in identified neurons following monocular deprivation and affected the maturation of dendritic spines, demonstrating its critical role in the plasticity of visual cortex circuits.

Nucleus basalis-enabled stimulus-specific plasticity in the visual cortex is mediated by astrocytes

Although cholinergic innervation of the cortex by the nucleus basalis (NB) is known to modulate cortical neuronal responses and instruct cortical plasticity, little is known about the underlying cellular mechanisms. Using cell-attached recordings in vivo, we demonstrate that electrical stimulation of the NB, paired with visual stimulation, can induce significant potentiation of visual responses in excitatory neurons of the primary visual cortex in mice. We further show with in vivo two-photon calcium imaging, ex vivo calcium imaging, and whole-cell recordings that this pairing-induced potentiation is mediated by direct cholinergic activation of primary visual cortex astrocytes via muscarinic AChRs. The potentiation is absent in conditional inositol 1,4,5 trisphosphate receptor type 2 KO mice, which lack astrocyte calcium activation, and is stimulus-specific, because pairing NB stimulation with a specific visual orientation reveals a highly selective potentiation of responses to the paired orientation compared with unpaired orientations. Collectively, these findings reveal a unique and surprising role for astrocytes in NB-induced stimulus-specific plasticity in the cerebral cortex.

Mechanisms of Plasticity in the Developing and Adult Visual Cortex

The visual cortex provides powerful evidence for experience-dependent plasticity during development, and for stimulus and reinforcement-dependent plasticity in adulthood. The synaptic and circuit mechanisms underlying such plasticity are being progressively understood. Increasing evidence supports the hypothesis that plasticity in both the developing and adult visual cortex is initiated by a transient reduction of inhibitory drive, and implemented by persistent changes at excitatory synapses. Developmental plasticity may be induced by alterations in the balance of activity from the two eyes and is implemented by a cascade of signals that lead to feedforward and feedback changes at synapses. Adult plasticity is imposed on mature synapses and requires additional neurotransmitter-dependent mechanisms that alter inhibition and subsequently response gain.

Direct modulation of GFAP-expressing glia in the arcuate nucleus bi-directionally regulates feeding

Multiple hypothalamic neuronal populations that regulate energy balance have been identified. Although hypothalamic glia exist in abundance and form intimate structural connections with neurons, their roles in energy homeostasis are less known. Here we show that selective Ca2+ activation of glia in the mouse arcuate nucleus (ARC) reversibly induces increased food intake while disruption of Ca2+ signaling pathway in ARC glia reduces food intake. The specific activation of ARC glia enhances the activity of agouti-related protein/neuropeptide Y (AgRP/NPY)-expressing neurons but induces no net response in pro-opiomelanocortin (POMC)-expressing neurons. ARC glial activation non-specifically depolarizes both AgRP/NPY and POMC neurons but a strong inhibitory input to POMC neurons balances the excitation. When AgRP/NPY neurons are inactivated, ARC glial activation fails to evoke any significant changes in food intake. Collectively, these results reveal an important role of ARC glia in the regulation of energy homeostasis through its interaction with distinct neuronal subtype-specific pathways. DOI: http://dx.doi.org/10.7554/eLife.18716.001

Imaging prior information in the brain

In making sense of the visual world, the brains processing is driven by two factors: the physical information provided by the eyes (“bottom-up” data) and the expectancies driven by past experience (“top-down” influences). We use degraded stimuli to tease apart the effects of bottom-up and top-down processes because they are easier to recognize with prior knowledge of undegraded images. Using machine learning algorithms, we quantify the amount of information that brain regions contain about stimuli as the subject learns the coherent images. Our results show that several distinct regions, including high-level visual areas and the retinotopic cortex, contain more information about degraded stimuli with prior knowledge. Critically, these regions are separate from those that exhibit classical priming, indicating that top-down influences are more than feature-based attention. Together, our results show how the neural processing of complex imagery is rapidly influenced by fleeting experiences.

Cell-specific modulation of plasticity and cortical state by cholinergic inputs to the visual cortex.

Acetylcholine (ACh) modulates diverse vital brain functions. Cholinergic neurons from the basal forebrain innervate a wide range of cortical areas, including the primary visual cortex (V1), and multiple cortical cell types have been found to be responsive to ACh. Here we review how different cell types contribute to different cortical functions modulated by ACh. We specifically focus on two major cortical functions: plasticity and cortical state. In layer II/III of V1, ACh acting on astrocytes and somatostatin-expressing inhibitory neurons plays critical roles in these functions. Cell type specificity of cholinergic modulation points towards the growing understanding that even diffuse neurotransmitter systems can mediate specific functions through specific cell classes and receptors.