Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing.

Perineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice.

Repressor element 1-silencing transcription factor drives the development of chronic pain states.

Chronic pain is an unmet clinical problem with vast individual, societal, and economic impact. Pathologic activity of the peripheral somatosensory afferents is one of the major drivers of chronic pain. This overexcitable state of somatosensory neurons is, in part, produced by the dysregulation of genes controlling neuronal excitability.

Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission.

The integration of somatosensory information is generally assumed to be a function of the central nervous system (CNS). Here we describe fully functional GABAergic communication within rodent peripheral sensory ganglia and show that it can modulate transmission of pain-related signals from the peripheral sensory nerves to the CNS. We found that sensory neurons express major proteins necessary for GABA synthesis and release and that sensory neurons released GABA in response to depolarization.

Sequential therapy of anti-Nogo-A antibody treatment and treadmill training leads to cumulative improvements after spinal cord injury in rats.

Intense training is the most clinically successful treatment modality following incomplete spinal cord injuries (SCIs). With the advent of plasticity enhancing treatments, understanding how treatments might interact when delivered in combination becomes critical. Here, we investigated a rational approach to sequentially combine treadmill locomotor training with antibody mediated suppression of the fiber growth inhibitory protein Nogo-A.

Role of gap junctions on synchronization in human neocortical networks.

Gap junctions (GJ) have been implicated in the synchronization of epileptiform activities induced by 4-aminopyrine (4AP) in slices from human epileptogenic cortex. Previous evidence implicated glial GJ to govern the frequency of these epileptiform events. The synchrony of these events (evaluated by the phase unlocking index, PUI) in adjacent areas however was attributed to neuronal GJ.

Different pharmacology of N-desmethylclozapine at human and rat M2 and M 4 mAChRs in neocortex.

Cholinergic transmission plays a pivotal role in learning, memory and cognition, and disturbances of cholinergic transmission have been implicated in neurological disorders including Alzheimer's disease, epilepsy and schizophrenia. Pharmacological alleviation of these diseases by drugs including N-desmethylclozapine (NDMC), promising in animal models, often fails in patients. We therefore compared the effects of NDMC on glutamatergic and GABAergic transmission in slices from rat and human neocortex.

Decrease of neocortical paired-pulse depression in GAERS and possible implication of gap junctions.

Thalamocortical slices are widely used to study thalamocortical relationships and absence epilepsy. However, it is still not known whether (1) intracortical synaptic transmission, in particular neocortical paired-pulse depression (PPD), is maintained in these slices and (2) whether PPD is altered in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS, a model of absence epilepsy for which cortico-thalamic loops are involved). Furthermore, while the involvement of gap junctions (GJ) in the mechanisms leading to epileptiform discharges has been intensively studied, little is known about their effect on intracortical transmission.

Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission.

Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission.

Bradykinin controls pool size of sensory neurons expressing functional δ-opioid receptors.

Analgesics targeting the δ-opioid receptor (DOR) may lead to fewer side effects than conventional opioid drugs, which mainly act on μ-opioid receptors (MOR), because of the less abundant expression of DOR in the CNS compared with MOR. Analgesic potential of DOR agonists increases after inflammation, an effect that may be mediated by DOR expressed in the peripheral sensory fibers. However, the expression of functional DOR at the plasma membrane of sensory neurons is controversial.

Thalamocortical relationships and network synchronization in a new genetic model "in mirror" for absence epilepsy.

Electroencephalographic generalized spike and wave discharges (SWD), the hallmark of human absence seizures, are generated in thalamocortical networks. However, the potential alterations in these networks in terms of the efficacy of the reciprocal synaptic activities between the cortex and the thalamus are not known in this pathology. Here, the efficacy of these reciprocal connections is assessed in vitro in thalamocortical slices obtained from BS/Orl mice, which is a new genetic model of absence epilepsy.

Triple cysteine module within M-type K+ channels mediates reciprocal channel modulation by nitric oxide and reactive oxygen species.

We have identified a new signaling role for nitric oxide (NO) in neurons from the trigeminal ganglia (TG). We show that in rat sensory neurons from the TG the NO donor, S-nitroso-N-acetyl-dl-penicillamine, inhibited M-current. This inhibitory effect was blocked by NO scavenging, while inhibition of NO synthases increased M-current, suggesting that tonic NO levels inhibit M-current in TG neurons.

M-Current Recording from Acute DRG Slices.

Electrophysiological recordings from an acutely sliced preparation provide information on ionic currents and excitability of native neurons under near physiological conditions. Although this technique is commonly used on central nervous system structures such as spinal cord and brain, structures within the peripheral nervous system (including sensory ganglia and fibers) have proven to be much more difficult to study in acute preparations. Here we describe a method for patch-clamp recordings from rat dorsal root ganglion (DRG) slices.

Evaluating reference genes to normalize gene expression in human epileptogenic brain tissues.

Several reference genes have been used to quantify gene expression in human epilepsy surgery tissue. However, their reliability has not been validated in detail, although this is crucial in interpreting epilepsy-related changes of gene expression. We evaluated 12 potential reference genes in neocortical tissues resected from patients with temporal lobe epilepsy (TLE) with either few or many seizures (n=6 each) and post mortem controls (n=6) using geNorm and NormFinder algorithms.

N-desmethylclozapine (NDMC) is an antagonist at the human native muscarinic M(1) receptor.

N-desmethylclozapine (NDMC) has been reported to display partial agonism at the human recombinant and rat native M(1) mAChR, a property suggested to contribute to the clinical efficacy of clozapine. However, the profile of action of NDMC at the human native M(1) mAChR has not been reported. The effect of NDMC on M(1) mAChR function was investigated in human native tissues by assessing its effect on (1) M(1) mAChR-mediated stimulation of [(35)S]-GTPgammaS-G(q/11)alpha binding to human post mortem cortical membranes and (2) the M(1) mAChR-mediated increase in neuronal firing in human neocortical slices.

[Cellular mechanisms of the epilepsies: In vitro studies on human tissue].

Background And Purpose: Animal models have provided very valuable data to specify the physiopathological mechanisms of the various forms of epilepsy. However, the question arises of knowing which of these experimental results are relevant to the human epileptic brain. The development of epileptic surgery makes it possible to directly study the functional properties of human brain tissue in vitro and to analyze the mechanisms underlying seizures and epileptogenesis.

Dysfunction of GABAA receptor glycolysis-dependent modulation in human partial epilepsy.

A reduction in GABAergic neurotransmission has been put forward as a pathophysiological mechanism for human epilepsy. However, in slices of human epileptogenic neocortex, GABAergic inhibition can be clearly demonstrated. In this article we present data showing an increase in the functional lability of GABAergic inhibition in epileptogenic tissue compared with nonepileptogenic human tissue.

Effects of gap junction blockers on human neocortical synchronization.

Field potentials and intracellular recordings were obtained from human neocortical slices to study the role of gap junctions (GJ) in neuronal network synchronization. First, we examined the effects of GJ blockers (i.e.

Effects in vitro and in vivo of a gap junction blocker on epileptiform activities in a genetic model of absence epilepsy.

We investigated the effects of carbenoxolone (CBX), a gap junctions (GJ) blocker, on epileptiform activities in vivo and in vitro. In a first series of experiments, i.p.

Waking selective neurons in the posterior hypothalamus and their response to histamine H3-receptor ligands: an electrophysiological study in freely moving cats.

Neurons which discharge selectively during waking (waking selective) have been found in the tuberomamillary nucleus (TM) and adjacent areas of the posterior hypothalamus. Although they share some electrophysiological properties with aminergic neurons, there is no direct evidence that they are histaminergic. We have recorded from posterior hypothalamic neurons during the sleep-wake cycle in freely moving cats, and investigated the effects on waking selective neurons of specific ligands of histaminergic H3-receptors, which autoregulate the activity of histaminergic neurons.