Stability of Conducting Polymer-Coated Carbon Microfibers for Long-Term Electrical Stimulation of Injured Neural Tissue.

Electroactive microfiber-based scaffolds aid neural tissue repair. Carbon microfibers (CMFs) coated with the conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly[(4-styrenesulfonic acid)--(maleic acid)] (PEDOT:PSS--MA) provide efficient support and guidance to regrowing axons across spinal cord lesions in rodents and pigs. We investigated the electrical and structural performance of PEDOT:PSS--MA-coated carbon MFs (PCMFs) for long-term, biphasic electrical stimulation (ES).

Neuropathological and Motor Impairments after Incomplete Cervical Spinal Cord Injury in Pigs.

Humans, primates, and rodents with cervical spinal cord injury (SCI) show permanent sensorimotor dysfunction of the upper/forelimb as consequence of axonal damage and local neuronal death. This work aimed at characterizing a model of cervical SCI in domestic pigs in which hemisection with excision of 1 cm of spinal cord was performed to reproduce the loss of neural tissue observed in human neuropathology. Posture and motor control were assessed over 3 months by scales and kinematics of treadmill locomotion.

Expression of the cold thermoreceptor TRPM8 in rodent brain thermoregulatory circuits.

The cold- and menthol-activated ion channel transient receptor potential channel subfamily M member 8 (TRPM8) is the principal detector of environmental cold in mammalian sensory nerve endings. Although it is mainly expressed in a subpopulation of peripheral sensory neurons, it has also been identified in non-neuronal tissues. Here, we show, by in situ hybridization (ISH) and by the analysis of transgenic reporter expression in two different reporter mouse strains, that TRPM8 is also expressed in the central nervous system.

Enhanced spinal cord microstimulation using conducting polymer-coated carbon microfibers.

Intraspinal microstimulation (ISMS) may help to restore motor functions after spinal cord injury. ISMS caudal to the lesion activates motoneurons and evokes selective movements with graded force in rats and other mammals. We investigated the safety and effectiveness of conducting polymer (CP)-coated carbon microfibers (CMFs) for ISMS.

Biofunctionalized Conducting Polymer/Carbon Microfiber Electrodes for Ultrasensitive Neural Recordings.

Unlabelled: Carbon microfibers (MFs) coated with conducting polymers may provide a solution for long-term recording of activity from individual or small groups of neurons. Attaching cell adhesion molecules to the electro-sensitive surface might further improve electrode-neuron contact, thus enhancing signal stability and fidelity. We fabricated biofunctionalized microelectrodes consisting of 7-μm diameter carbon MFs coated with poly(3,4-ethylenedioxythiophene) doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)] (

Pedot: PSS-co-MA), and linked N-Cadherin to the polymer surface.

Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's disease.

A disintegrin and metalloproteinase 10 (ADAM10), a disintegrin and metalloproteinase that resides in the postsynaptic densities (PSDs) of excitatory synapses, has previously been shown to limit β-amyloid peptide (Aβ) formation in Alzheimer's disease (AD). ADAM10 also plays a critical role in regulating functional membrane proteins at the synapse. Using human hippocampal homogenates, we found that ADAM10 removal from the plasma membrane was mediated by clathrin-dependent endocytosis.

The influence of cold temperature on cellular excitability of hippocampal networks.

The hippocampus plays an important role in short term memory, learning and spatial navigation. A characteristic feature of the hippocampal region is its expression of different electrical population rhythms and activities during different brain states. Physiological fluctuations in brain temperature affect the activity patterns in hippocampus, but the underlying cellular mechanisms are poorly understood.

Blocking ADAM10 synaptic trafficking generates a model of sporadic Alzheimer's disease.

We describe here an innovative, non-transgenic animal model of Alzheimer's disease. This model mimics early stages of sporadic disease, which represents the vast majority of cases. The model was obtained by interfering with the complex between a disintegrin and metalloproteinase domain containing protein 10 (ADAM10), the main α-secretase candidate, and its partner, synapse-associated protein 97, a protein of the postsynaptic density-membrane associated guanylate kinase family.

Learning, AMPA receptor mobility and synaptic plasticity depend on n-cofilin-mediated actin dynamics.

Neuronal plasticity is an important process for learning, memory and complex behaviour. Rapid remodelling of the actin cytoskeleton in the postsynaptic compartment is thought to have an important function for synaptic plasticity. However, the actin-binding proteins involved and the molecular mechanisms that in vivo link actin dynamics to postsynaptic physiology are not well understood.

A postsynaptic signaling pathway that may account for the cognitive defect due to IL1RAPL1 mutation.

Background: Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1) gene mutations are associated with cognitive impairment ranging from nonsyndromic X-linked mental retardation to autism. IL1RAPL1 belongs to a novel family of Toll/IL-1 receptors, whose expression in the brain is upregulated by neuronal activity. Currently, very little is known about the function of this protein.

ERK activation in axonal varicosities modulates presynaptic plasticity in the CA3 region of the hippocampus through synapsin I.

Activity-dependent changes in the strength of synaptic connections in the hippocampus are central for cognitive processes such as learning and memory storage. In this study, we reveal an activity-dependent presynaptic mechanism that is related to the modulation of synaptic plasticity. In acute mouse hippocampal slices, high-frequency stimulation (HFS) of the mossy fiber (MF)-CA3 pathway induced a strong and transient activation of extracellular-regulated kinase (ERK) in MF giant presynaptic terminals.

Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) controls activation of extracellular signal-regulated kinase (ERK) signaling in the striatum and long-term behavioral responses to cocaine.

Background: Ras-extracellular signal-regulated kinase (Ras-ERK) signaling is central to the molecular machinery underlying cognitive functions. In the striatum, ERK1/2 kinases are co-activated by glutamate and dopamine D1/5 receptors, but the mechanisms providing such signaling integration are still unknown. The Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1), a neuronal specific activator of Ras-ERK signaling, is a likely candidate for coupling these neurotransmitter signals to ERK kinases in the striatonigral medium spiny neurons (MSN) and for modulating behavioral responses to drug abuse such as cocaine.

Synaptic vesicle docking: sphingosine regulates syntaxin1 interaction with Munc18.

Consensus exists that lipids must play key functions in synaptic activity but precise mechanistic information is limited. Acid sphingomyelinase knockout mice (ASMko) are a suitable model to address the role of sphingolipids in synaptic regulation as they recapitulate a mental retardation syndrome, Niemann Pick disease type A (NPA), and their neurons have altered levels of sphingomyelin (SM) and its derivatives. Electrophysiological recordings showed that ASMko hippocampi have increased paired-pulse facilitation and post-tetanic potentiation.

Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior.

Profilins are actin binding proteins essential for regulating cytoskeletal dynamics, however, their function in the mammalian nervous system is unknown. Here, we provide evidence that in mouse brain profilin1 and profilin2 have distinct roles in regulating synaptic actin polymerization with profilin2 preferring a WAVE-complex-mediated pathway. Mice lacking profilin2 show a block in synaptic actin polymerization in response to depolarization, which is accompanied by increased synaptic excitability of glutamatergic neurons due to higher vesicle exocytosis.

Augmentation of excitability in the hippocampus of juvenile rat.

The short-term plasticity of synaptic transmission has usually been related to neurotransmitter release-dependent processes. In this work, we describe a calcium- and release-independent augmentation of the fiber volley (FVA) that appears during stimulation of the Wistar rat commissural/Schaffer collateral afferents at 10-Hz. Among the possible mechanisms involved in this phenomenon, an increment in sodium channel density or the facilitation of recovery from inactivation does not seem to be responsible for this effect since the depolarization rate of the somatic action potentials (APs) of CA3 pyramidal cells decreases during the 10-Hz stimulation.

Characterization of release-independent short-term depression in the juvenile rat hippocampus.

Short-term depression strongly influences neuronal activity in cerebral circuits and contributes to low-pass temporal filtering of information. In this work, we show that synaptic depression evoked by stimulation of commissural-Schaffer collateral afferents at 10 Hz is associated with a reduction of the fibre volley. This depression of action potentials is also evident in the absence of extracellular Ca(2+), which underlies its release-independent nature.

Age-dependent alterations of long-term synaptic plasticity in thyroid-deficient rats.

Thyroid hormone deficiency during a critical period of development profoundly affects cognitive functions such as attention, learning, and memory, but the synaptic alterations underlying these deficits remain unexplored. The present study examines the effect of congenital hypothyroidism on long-term synaptic plasticity. This plasticity is believed to be essential for learning and memory and for activity-dependent regulation of synapse formation in the developing brain.

[Short term synaptic plasticity].

Introduction: At many chemical synapses, the amount of transmitter released by each action potential can increase or decrease markedly after the onset of specific temporal patterns of activity.

Objectives: This review focuses on mechanisms and functions of short term presynaptic plasticity that last from milliseconds to minutes. The short term enhancement of neurotransmitter release is due to three calcium dependent presynaptic processes differing in their durations: about one second or less (facilitation), about 30 seconds (augmentation) and several minutes (post tetanic potentiation).

Thyroid hormone regulates neurotransmitter release in neonatal rat hippocampus.

Thyroid hormone is essential for the normal maturation and function of the mammalian CNS. Thyroid hormone deficiency during a critical period of development profoundly affects cognitive functions such as learning and memory. However, the possible electrophysiological alterations that could underlie these learning deficits in hypothyroid animals remain largely unexplored.