In patients with damage to the primary visual cortex (V1), residual vision can guide goal-directed movements to targets in the blind field without awareness. This phenomenon has been termed ...blindsight, and its neural mechanisms are controversial. There should be visual pathways to the higher visual cortices bypassing V1, however some literature propose that the signal is mediated by the superior colliculus (SC) and pulvinar, while others claim the dorsal lateral geniculate nucleus (dLGN) transmits the signal. Here, we directly test the role of SC to ventrolateral pulvinar (vlPul) pathway in blindsight monkeys. Pharmacological inactivation of vlPul impairs visually guided saccades (VGS) in the blind field. Selective and reversible blockade of the SC-vlPul pathway by combining two viral vectors also impairs VGS. With these results we claim the SC-vlPul pathway contributes to blindsight. The discrepancy would be due to the extent of retrograde degeneration of dLGN and task used for assessment.
Abstract
Decision-making via monitoring others’ actions is a cornerstone of interpersonal exchanges. Although the ventral premotor cortex (PMv) and the medial prefrontal cortex (MPFC) are cortical ...nodes in social brain networks, the two areas are rarely concurrently active in neuroimaging, inviting the hypothesis that they are functionally independent. Here we show in macaques that the ability of the MPFC to monitor others’ actions depends on input from the PMv. We found that delta-band coherence between the two areas emerged during action execution and action observation. Information flow especially in the delta band increased from the PMv to the MPFC as the biological nature of observed actions increased. Furthermore, selective blockade of the PMv-to-MPFC pathway using a double viral vector infection technique impaired the processing of observed, but not executed, actions. These findings demonstrate that coordinated activity in the PMv-to-MPFC pathway has a causal role in social action monitoring.
Postsynaptic density (PSD)-95, the most abundant postsynaptic scaffolding protein, plays a pivotal role in synapse development and function. Continuous palmitoylation cycles on PSD-95 are essential ...for its synaptic clustering and regulation of AMPA receptor function. However, molecular mechanisms for palmitate cycling on PSD-95 remain incompletely understood, as PSD-95 depalmitoylating enzymes remain unknown. Here, we isolated 38 mouse or rat serine hydrolases and found that a subset specifically depalmitoylated PSD-95 in heterologous cells. These enzymes showed distinct substrate specificity. α/β-Hydrolase domain-containing protein 17 members (ABHD17A, 17B, and 17C), showing the strongest depalmitoylating activity to PSD-95, showed different localization from other candidates in rat hippocampal neurons, and were distributed to recycling endosomes, the dendritic plasma membrane, and the synaptic fraction. Expression of ABHD17 in neurons selectively reduced PSD-95 palmitoylation and synaptic clustering of PSD-95 and AMPA receptors. Furthermore, taking advantage of the acyl-PEGyl exchange gel shift (APEGS) method, we quantitatively monitored the palmitoylation stoichiometry and the depalmitoylation kinetics of representative synaptic proteins, PSD-95, GluA1, GluN2A, mGluR5, Gαq, and HRas. Unexpectedly, palmitate on all of them did not turn over in neurons. Uniquely, most of the PSD-95 population underwent rapid palmitoylation cycles, and palmitate cycling on PSD-95 decelerated accompanied by its increased stoichiometry as synapses developed, probably contributing to postsynaptic receptor consolidation. Finally, inhibition of ABHD17 expression dramatically delayed the kinetics of PSD-95 depalmitoylation. This study suggests that local palmitoylation machinery composed of synaptic DHHC palmitoylating enzymes and ABHD17 finely controls the amount of synaptic PSD-95 and synaptic function.
Protein palmitoylation, the most common lipid modification, dynamically regulates neuronal protein localization and function. Its unique reversibility is conferred by DHHC-type palmitoyl acyl transferases (palmitoylating enzymes) and still controversial palmitoyl-protein thioesterases (depalmitoylating enzymes). Here, we identified the membrane-anchored serine hydrolases, ABHD17A, 17B, and 17C, as the physiological PSD-95 depalmitoylating enzymes that regulate PSD-95 palmitoylation cycles in neurons. This study describes the first direct evidence for the neuronal depalmitoylating enzyme and provides a new aspect of the dynamic regulatory mechanisms of synaptic development and synaptic plasticity. In addition, our established APEGS assay, which provides unbiased and quantitative information about the palmitoylation state and dynamics, revealed the distinct regulatory mechanisms for synaptic palmitoylation.
Body fluid conditions are continuously monitored in the brain to regulate thirst and salt-appetite sensations. Angiotensin II drives both thirst and salt appetite; however, the neural mechanisms ...underlying selective water- and/or salt-intake behaviors remain unknown. Using optogenetics, we show that thirst and salt appetite are driven by distinct groups of angiotensin II receptor type 1a-positive excitatory neurons in the subfornical organ. Neurons projecting to the organum vasculosum lamina terminalis control water intake, while those projecting to the ventral part of the bed nucleus of the stria terminalis control salt intake. Thirst-driving neurons are suppressed under sodium-depleted conditions through cholecystokinin-mediated activation of GABAergic neurons. In contrast, the salt appetite-driving neurons were suppressed under dehydrated conditions through activation of another population of GABAergic neurons by Na
signals. These distinct mechanisms in the subfornical organ may underlie the selective intakes of water and/or salt and may contribute to body fluid homeostasis.
The basal ganglia are critical for the control of motor behaviors and for reinforcement learning. Here, we demonstrate in rats that primary and secondary motor areas (M1 and M2) make functional ...synaptic connections in the globus pallidus (GP), not usually thought of as an input site of the basal ganglia. Morphological observation revealed that the density of axonal boutons from motor cortices in the GP was 47% and 78% of that in the subthalamic nucleus (STN) from M1 and M2, respectively. Cortical excitation of GP neurons was comparable to that of STN neurons in slice preparations. FoxP2-expressing arkypallidal neurons were preferentially innervated by the motor cortex. The connection probability of cortico-pallidal innervation was higher for M2 than M1. These results suggest that cortico-pallidal innervation is an additional excitatory input to the basal ganglia, and that it can affect behaviors via the cortex-basal ganglia-thalamus motor loop.
Abstract
The control of water-intake behavior is critical for life because an excessive water intake induces pathological conditions, such as hyponatremia or water intoxication. However, the brain ...mechanisms controlling water intake currently remain unclear. We previously reported that thirst-driving neurons (water neurons) in the subfornical organ (SFO) are cholecystokinin (CCK)-dependently suppressed by GABAergic interneurons under Na-depleted conditions. We herein show that CCK-producing excitatory neurons in the SFO stimulate the activity of GABAergic interneurons via CCK-B receptors. Fluorescence-microscopic Ca
2+
imaging demonstrates two distinct subpopulations in CCK-positive neurons in the SFO, which are persistently activated under hyponatremic conditions or transiently activated in response to water drinking, respectively. Optical and chemogenetic silencings of the respective types of CCK-positive neurons both significantly increase water intake under water-repleted conditions. The present study thus reveals CCK-mediated neural mechanisms in the central nervous system for the control of water-intake behaviors.
Optogenetics has become an indispensable tool for investigating brain functions. Although non-human primates are particularly useful models for understanding the functions and dysfunctions of the ...human brain, application of optogenetics to non-human primates is still limited. In the present study, we generate an effective adeno-associated viral vector serotype DJ to express channelrhodopsin-2 (ChR2) under the control of a strong ubiquitous CAG promoter and inject into the somatotopically identified forelimb region of the primary motor cortex in macaque monkeys. ChR2 is strongly expressed around the injection sites, and optogenetic intracortical microstimulation (oICMS) through a homemade optrode induces prominent cortical activity: Even single-pulse, short-duration oICMS evokes long-lasting repetitive firings of cortical neurons. In addition, oICMS elicits distinct forelimb movements and muscle activity, which are comparable to those elicited by conventional electrical ICMS. The present study removes obstacles to optogenetic manipulation of neuronal activity and behaviors in non-human primates.
The value of one's own reward is affected by the reward of others, serving as a source for envy. However, it is not known which neural circuits mediate such socially subjective value modulation. ...Here, we chemogenetically dissected the circuit from the medial prefrontal cortex (MPFC) to the lateral hypothalamus (LH) while male macaques were presented with visual stimuli that concurrently signaled the prospects of one's own and others' rewards. We found that functional disconnection between the MPFC and LH rendered animals significantly less susceptible to others' but not one's own reward prospects. In parallel with this behavioral change, inter-areal coordination, as indexed by coherence and Granger causality, decreased primarily in the delta and theta bands. These findings demonstrate that the MPFC-to-LH circuit plays a crucial role in carrying information about upcoming other-rewards for subjective reward valuation in social contexts.
Thirst and salt appetite are temporarily suppressed after water and salt ingestion, respectively, before absorption; however, the underlying neural mechanisms remain unclear. The parabrachial nucleus ...(PBN) is the relay center of ingestion signals from the digestive organs. We herein identify two distinct neuronal populations expressing cholecystokinin (Cck) mRNA in the lateral PBN that are activated in response to water and salt intake, respectively. The two Cck neurons in the dorsal-lateral compartment of the PBN project to the median preoptic nucleus and ventral part of the bed nucleus of the stria terminalis, respectively. The optogenetic stimulation of respective Cck neurons suppresses thirst or salt appetite under water- or salt-depleted conditions. The combination of optogenetics and in vivo Ca2+ imaging during ingestion reveals that both Cck neurons control GABAergic neurons in their target nuclei. These findings provide the feedback mechanisms for the suppression of thirst and salt appetite after ingestion.
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•Thirst and salt appetite are temporarily suppressed after water and salt ingestion, respectively•Two distinct subpopulations of LPBN Cck neurons are activated by water or salt ingestion•One population stimulates GABA neurons in the MnPO and the other those in the vBNST•These two pathways are involved in the suppression of thirst or salt appetite
Thirst and salt appetite are controlled based not only on body fluid conditions but also on ingestion. Matsuda et al. reveal that water and salt ingestion signals are relayed by distinct LPBN Cck neurons to GABAergic neurons in the MnPO and vBNST to suppress thirst and salt appetite, respectively.
Abstract
We describe the synthesis and visible-light CO
2
photoreduction catalytic properties of a three-component composite consisting of AgI, AgIO
3
, and single-walled carbon nanotubes (SWCNTs). ...The catalyst is synthesized by immersing SWCNTs encapsulating iodine molecules in AgNO
3
aqueous solution, during which neutral iodine (I
2
) molecules encapsulated in SWCNTs transform disproportionately to I
5+
(AgIO
3
) and I
−
(AgI), as revealed from the characterization of the composite by Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. In addition, photoirradiation experiments using a solar-simulator (AM1.5G) showed that the obtained three-component composite works as a CO
2
photoreduction catalyst under visible light despite the wide band gap of AgIO
3
, suggesting possible transfer of the visible light-excited electron from AgI via SWCNTs.
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