Current opinion in neurobiology
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Curr. Opin. Neurobiol. · Feb 2015
ReviewAntidepressant actions of ketamine: from molecular mechanisms to clinical practice.
In the past decade the emergence of glutamate N-methyl-d-aspartate (NMDA) receptor blockers such as ketamine as fast-acting antidepressants fostered a major conceptual advance by demonstrating the possibility of a rapid antidepressant response. This discovery brings unique mechanistic insight into antidepressant action, as there is a substantial amount of basic knowledge on glutamatergic neurotransmission and how blockade of NMDA receptors may elicit plasticity. The combination of this basic knowledge base and the growing clinical findings will facilitate the development of novel fast acting antidepressants.
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The expression of Nogo-A and the receptor NgR1 limits the recovery of adult mammals from central nervous system injury. Multiple studies have demonstrated efficacy from targeting this pathway for functional recovery and neural repair after spinal cord trauma, ischemic stroke, optic nerve injury and models of multiple sclerosis. ⋯ It has been recognized that neural repair involves plasticity, sprouting and regeneration. A physiologic role for Nogo-A and NgR1 has been documented in the restriction of experience-dependent plasticity with maturity, and the stability of synaptic, dendritic and axonal anatomy.
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Curr. Opin. Neurobiol. · Aug 2014
ReviewThe multifaceted roles of Slits and Robos in cortical circuits: from proliferation to axon guidance and neurological diseases.
Slit repulsion, mediated by Robo receptors, is known to play a major role in axon guidance in the nervous system. However, recent studies have revealed that in the mammalian cortex these molecules are highly versatile and that their function extends far beyond axon guidance. ⋯ These findings also suggest that Slit and Robos have influenced the evolution of cortical circuits. Last, novel genetic evidence associates various neurological disorders, such as autism, to abnormal Slit/Robo signaling.
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Curr. Opin. Neurobiol. · Jun 2014
ReviewInterneuronal GABAA receptors inside and outside of synapses.
About 20% of the total number of neurons in the brain are interneurons (INs) that utilize GABA as their neurotransmitter. The receptors for GABA have been well studied in principal cells, but INs also express GABA receptors, in particular the GABAA type (GABAARs), which may also be activated in an autocrine manner by the transmitter released by the INs themselves. As more and more neurological and psychiatric disorders are being discovered to be linked to malfunction or deficits of INs, this review will cover how INs communicate with each other through the activation of synaptic and extrasynaptic GABAARs. The properties of GABAARs specific to INs may differ significantly from those found on principal cells to open the prospect of developing IN-specific drugs.
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Curr. Opin. Neurobiol. · Jun 2014
ReviewSpatiotemporal specificity in cholinergic control of neocortical function.
Cholinergic actions are critical for normal cortical cognitive functions. The release of acetylcholine (ACh) in neocortex and the impact of this neuromodulator on cortical computations exhibit remarkable spatiotemporal precision, as required for the regulation of behavioral processes underlying attention and learning. ⋯ We also review recent studies suggesting that the modulatory influences of ACh on the properties of cortical neurons can have the necessary temporal dynamic range, emphasizing evidence of powerful interneuron subtype-specific effects. We discuss areas that require further investigation and point to technical advances in molecular and genetic manipulations that promise to make headway in understanding the neural bases of cholinergic modulation of cortical cognitive operations.