Parvalbumin-expressing interneurons can act solo while somatostatin-expressing interneurons act in chorus in most cases on cortical pyramidal cells.

Neural circuits in the cerebral cortex consist primarily of excitatory pyramidal (Pyr) cells and inhibitory interneurons. Interneurons are divided into several subtypes, in which the two major groups are those expressing parvalbumin (PV) or somatostatin (SOM). These subtypes of interneurons are reported to play distinct roles in tuning and/or gain of visual response of pyramidal cells in the visual cortex.

3D clustering of GABAergic neurons enhances inhibitory actions on excitatory neurons in the mouse visual cortex.

Neocortical neurons with similar functional properties assemble into spatially coherent circuits, but it remains unclear how inhibitory interneurons are organized. We applied in vivo two-photon functional Ca(2+) imaging and whole-cell recording of synaptic currents to record visual responses of cortical neurons and analyzed their spatial arrangements. GABAergic interneurons were clustered in the 3D space of the mouse visual cortex, and excitatory neurons located within the clusters (insiders) had a lower amplitude and sharper orientation tuning of visual responses than outsiders.

Curtailing effect of awakening on visual responses of cortical neurons by cholinergic activation of inhibitory circuits.

Visual responsiveness of cortical neurons changes depending on the brain state. Neural circuit mechanism underlying this change is unclear. By applying the method of in vivo two-photon functional calcium imaging to transgenic rats in which GABAergic neurons express fluorescent protein, we analyzed changes in visual response properties of cortical neurons when animals became awakened from anesthesia.

NSF workshop report: discovering general principles of nervous system organization by comparing brain maps across species.

Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene-structure-function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system 'maps' comprising molecular, anatomical, and physiological data.

NSF workshop report: discovering general principles of nervous system organization by comparing brain maps across species.

Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene-structure-function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system 'maps' comprising molecular, anatomical, and physiological data.

Reciprocal Homosynaptic and heterosynaptic long-term plasticity of corticogeniculate projection neurons in layer VI of the mouse visual cortex.

Most neurons in layer VI of the visual cortex project to the dorsal lateral geniculate nucleus (dLGN). These corticogeniculate projection neurons (CG cells) receive top-down synaptic inputs from upper layers (ULs) and bottom-up inputs from the underlying white matter (WM). Use-dependent plasticity of these synapses in layer VI of the cortex has received less attention than in other layers.

Cell type-specific, presynaptic LTP of inhibitory synapses on fast-spiking GABAergic neurons in the mouse visual cortex.

Properties and plasticity of inhibitory synapses on fast-spiking (FS) GABAergic (FS-GABA) interneurons in layer II/III of the mouse visual cortex were examined in cortical slices by whole-cell recordings of IPSCs or IPSPs evoked by activation of presynaptic FS or non-FS GABAergic interneurons. Unitary IPSCs (uIPSCs) evoked by action potentials of FS-GABA neurons have shorter onset latency, faster rising slope, higher peak amplitude, and faster decay time than those evoked by action potentials of non-FS-GABA neurons. Tetanic activation of presynaptic FS-GABA neurons induced long-term potentiation (LTP) of uIPSCs, whereas that of presynaptic non-FS-GABA neurons did not induce LTP, indicating that long-term plasticity of inhibitory synapses on FS-GABA neurons is pathway specific.

Selective control of inhibitory synapse development by Slitrk3-PTPδ trans-synaptic interaction.

Balanced development of excitatory and inhibitory synapses is required for normal brain function, and an imbalance in this development may underlie the pathogenesis of many neuropsychiatric disorders. Compared with the many identified trans-synaptic adhesion complexes that organize excitatory synapses, little is known about the organizers that are specific for inhibitory synapses. We found that Slit and NTRK-like family member 3 (Slitrk3) actS as a postsynaptic adhesion molecule that selectively regulates inhibitory synapse development via trans-interaction with axonal tyrosine phosphatase receptor PTPδ.

Neuroscience in recession?

As the global financial downturn continues, its impact on neuroscientists - both on an individual level and at the level of their research institute - becomes increasingly apparent. How is the economic crisis affecting neuroscience funding, career prospects, international collaborations and scientists' morale in different parts of the world? Nature Reviews Neuroscience gauged the opinions of a number of leading neuroscientists: the President of the Society for Neuroscience, the President Elect of the British Neuroscience Association, the former President of the Japan Neuroscience Society, the President of the Federation of European Neuroscience Societies and the Director of the US National Institute of Mental Health. Their responses provide interesting and important insights into the regional impact of the global financial downturn, with some causes for optimism for the future of neuroscience research.

Laminar-specific maturation of GABAergic transmission and susceptibility to visual deprivation are related to endocannabinoid sensitivity in mouse visual cortex.

The developmental period when neuronal responses are modified by visual experience is reported to start and end earlier in layer 4 than in layer 2/3 of the visual cortex, and the maturation of GABAergic inhibitory circuits is suggested to determine the timing of this period. Here, we examine whether the laminar difference in such timing corresponds to a difference in the time course of the functional maturation of GABAergic synaptic transmission to star pyramidal and pyramidal cells in layers 4 and 2/3, respectively, of the mouse visual cortex and whether the development of the strength of GABAergic transmission is affected by visual deprivation in a laminar-specific manner. Our analysis of developmental changes in inhibitory postsynaptic currents of star pyramidal and pyramidal cells evoked by electrical stimulation of afferents or action potentials of fast-spiking GABAergic neurons revealed that there was a sequential maturation of GABAergic function from layers 4 to 2/3.

Ephrin-A5 and EphA5 interaction induces synaptogenesis during early hippocampal development.

Background: Synaptogenesis is a fundamental step in neuronal development. For spiny glutamatergic synapses in hippocampus and cortex, synaptogenesis involves adhesion of pre and postsynaptic membranes, delivery and anchorage of pre and postsynaptic structures including scaffolds such as PSD-95 and NMDA and AMPA receptors, which are glutamate-gated ion channels, as well as the morphological maturation of spines. Although electrical activity-dependent mechanisms are established regulators of these processes, the mechanisms that function during early development, prior to the onset of electrical activity, are unclear.

The maturation of GABAergic transmission in visual cortex requires endocannabinoid-mediated LTD of inhibitory inputs during a critical period.

Endocannabinoids are widely regarded as negative modulators of presynaptic release. Here, we present evidence that in visual cortex endocannabinoids are crucial for the maturation of GABAergic release. We found that between eye opening and puberty, release changes from an immature state with high release probability, short-term depression (STD), and high release variability during irregular patterned activity, to a mature state with reduced release probability, STD, and variability.

Difference in binocularity and ocular dominance plasticity between GABAergic and excitatory cortical neurons.

Neuronal circuits in the cerebral cortex consist mainly of glutamatergic/excitatory and GABAergic/inhibitory neurons. In the visual cortex, the binocular responsiveness of neurons is modified by monocular visual deprivation during the critical period of postnatal development. Although GABAergic neurons are considered to play a key role in the expression of the critical period, it is not known whether their binocular responsiveness and ocular dominance plasticity are different from those of excitatory neurons.

Antibody to varicella-zoster virus immediate-early protein 62 augments allodynia in zoster via brain-derived neurotrophic factor.

Varicella-zoster virus (VZV) expresses immediate-early protein 62 (IE62), and zoster is associated with neuropathic pain. Brain-derived neurotrophic factor (BDNF) is involved in the neuronal mechanism underlying pain hypersensitivity. Zoster is associated with prodrome and the robust production of booster antibody to VZV.

Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility.

Mutations in EFHC1 gene have been previously reported in patients with epilepsies, including those with juvenile myoclonic epilepsy. Myoclonin1, also known as mRib72-1, is encoded by the mouse Efhc1 gene. Myoclonin1 is dominantly expressed in embryonic choroid plexus, post-natal ependymal cilia, tracheal cilia and sperm flagella.

Roles of endocannabinoids in heterosynaptic long-term depression of excitatory synaptic transmission in visual cortex of young mice.

Tetanic stimulation of one of two afferent pathways converging to neurons in the visual cortex induces long-term depression (LTD) of synaptic transmission in the other, nonactivated pathway under a certain condition. This form of synaptic plasticity called heterosynaptic LTD (hetero-LTD) was not systematically investigated in previous studies, whereas homosynaptic LTD has been extensively studied. To determine whether hetero-LTD is induced in visual cortical slices of mice and, if so, through what mechanisms, we recorded EPSPs evoked in layer II/III neurons by alternating test stimulation of two sites in layer IV at 0.

Regulation of excitability and plasticity by endocannabinoids and PKA in developing hippocampus.

The activity-dependent strengthening and weakening of synaptic transmission are hypothesized to be the basis of not only memory and learning but also the refinement of neural circuits during development. Here we report that, in the developing CA1 area of the hippocampus, endocannabinoid (eCB)-mediated heterosynaptic long-term depression (LTD) of glutamatergic excitatory synaptic transmission is associated with PKA-mediated homosynaptic long-term potentiation (LTP). This form of LTD was dominant at postnatal days 2-10 (P2-P10), attenuated during development, and finally disappeared in the mature hippocampus.

Metabotropic glutamate receptor type 5-dependent long-term potentiation of excitatory synapses on fast-spiking GABAergic neurons in mouse visual cortex.

Long-term potentiation (LTP) of excitatory synapses on GABAergic neurons in layer II/III of visual cortical slices was examined in GAD67-GFP knock-in mice by whole-cell recordings of EPSPs evoked by layer IV stimulation. Theta burst stimulation (TBS) paired with postsynaptic depolarization induced LTP in 14 of 19 fast-spiking GABAergic (FS-GABA) neurons, whereas only in 6 of 17 non-FS GABAergic neurons. The mean magnitude of LTP in the former cell group was larger than that in the latter.

A local reduction in cortical GABAergic synapses after a loss of endogenous brain-derived neurotrophic factor, as revealed by single-cell gene knock-out method.

To address questions of whether brain-derived neurotrophic factor (BDNF) released from active excitatory neurons acts locally only on GABAergic presynaptic terminals contacting these neurons or generally also on GABAergic terminals contacting other inactive neurons, we developed a single-cell gene knock-out method in organotypic slice culture of visual cortex of floxed BDNF transgenic mice. A biolistic transfection of Cre recombinase with green fluorescence protein (GFP) plasmids to layer II/III of the cortex resulted in loss of BDNF in a single neuron or a small number of neurons, which expressed GFP at 13-14 d in vitro. Analysis with in situ hybridization and immunohistochemistry confirmed that neurons expressing GFP lacked BDNF mRNA and protein, respectively.

GABAergic neurons are less selective to stimulus orientation than excitatory neurons in layer II/III of visual cortex, as revealed by in vivo functional Ca2+ imaging in transgenic mice.

Most neurons in the visual cortex are selectively responsive to visual stimulation of a narrow range of orientations, and GABAergic neurons are considered to play a role in the formation of such orientation selectivity. This suggests that response properties of GABAergic neurons may be different from those of excitatory neurons. This view remains unproved, however.

Bidirectional trafficking of prostaglandin E2 receptors involved in long-term potentiation in visual cortex.

Although prostaglandin E2 (PGE2) has a broad spectrum of biological activities that have been confirmed by previous studies, the roles of PGE2 in synaptic plasticity such as long-term potentiation (LTP) in the CNS have yet to be characterized in detail. The present results of electrophysiological and biochemical studies indicated that PGE2 is actually produced in acute visual cortex slices in response to theta-burst stimulation (TBS) and is involved postsynaptically in TBS-induced LTP. RNA interference (RNAi) for PGE2 receptor subtypes EP2 and EP3, which are known to upregulate and downregulate the level of cAMP, respectively, induced significant decreases and increases of LTP, respectively.

Recovery of binocular responses after brief monocular deprivation in kittens.

Monocular deprivation induces a rapid ocular dominance change in the developing visual cortex. The early phase of the change is supposed to be labile and stabilized later by consolidation processes. To test the stability of early ocular dominance change, we examined whether binocular responses of cortical neurons can recover after a brief monocular deprivation in anesthetized and paralyzed kittens in which ocular dominance plasticity does not operate.

Difference in trafficking of brain-derived neurotrophic factor between axons and dendrites of cortical neurons, revealed by live-cell imaging.

Background: Brain-derived neurotrophic factor (BDNF), which is sorted into a regulated secretory pathway of neurons, is supposed to act retrogradely through dendrites on presynaptic neurons or anterogradely through axons on postsynaptic neurons. Depending on which is the case, the pattern and direction of trafficking of BDNF in dendrites and axons are expected to be different. To address this issue, we analyzed movements of green fluorescent protein (GFP)-tagged BDNF in axons and dendrites of living cortical neurons by time-lapse imaging.

NMDA receptor-dependent synaptic translocation of insulin receptor substrate p53 via protein kinase C signaling.

The activity-dependent remodeling of postsynaptic structure is a fundamental process underlying learning and memory. Insulin receptor substrate p53 (IRSp53), a key player in cytoskeletal dynamics, is enriched in the postsynaptic density (PSD) fraction, but its significance in synaptic functions remains unclear. We report here that IRSp53 is accumulated rapidly at the postsynaptic sites of cultured hippocampal neurons after glutamate or NMDA stimulation in an actin cytoskeleton-dependent manner.

RNAi-induced gene silencing by local electroporation in targeting brain region.

Genetic manipulation for "knockout" (KO) is a useful tool for characterizing a target gene. However, its shortcomings that need to be overcome hinder its easy and ready usage in ordinary laboratories. Here we describe a knockdown technique termed the RNA interference (RNAi)-induced gene silencing by local electroporation (RISLE).