Grid cell disruption in a mouse model of early Alzheimer's disease reflects reduced integration of self-motion cues.

Converging evidence from human and rodent studies suggests that disrupted grid cell coding in the medial entorhinal cortex (MEC) underlies path integration behavioral deficits during early Alzheimer's disease (AD). However, grid cell firing relies on both self-motion cues and environmental features, and it remains unclear whether disrupted grid coding can account for specific path integration deficits reported during early AD. Here, we report in the J20 transgenic amyloid beta (Aβ) mouse model of early AD that grid cells were spatially unstable toward the center of the arena, had qualitatively different spatial components that aligned parallel to the borders of the environment, and exhibited impaired integration of distance traveled via reduced theta phase precession.

TRPC4 Channel Knockdown in the Hippocampal CA1 Region Impairs Modulation of Beta Oscillations in Novel Context.

Hippocampal local field potentials (LFP) are highly related to behavior and memory functions. It has been shown that beta band LFP oscillations are correlated with contextual novelty and mnemonic performance. Evidence suggests that changes in neuromodulators, such as acetylcholine and dopamine, during exploration in a novel environment underlie changes in LFP.

Persistent Firing in Hippocampal CA1 Pyramidal Cells in Young and Aged Rats.

Persistent neuronal firing is often observed in working memory and temporal association tasks both in humans and animals, and is believed to retain necessary information in these tasks. We have reported that hippocampal CA1 pyramidal cells are able to support persistent firing through intrinsic mechanisms in the presence of cholinergic agonists. However, it still remains largely unknown how persistent firing is affected by the development of animals and aging.

Social Cognition and Interaction Training (SCIT) versus Training in Affect Recognition (TAR) in patients with schizophrenia: A randomized controlled trial.

Introduction: Training in Affect Recognition (TAR) is a "targeted" and computer-aided program that has been shown to effectively attenuate facial affect recognition deficits and improve social functioning in patients with schizophrenia. Social Cognition and Interaction Training (SCIT) is a group "broad-based" intervention, that has also been shown to improve emotion recognition, theory of mind (ToM), and social functioning. To date, no study has compared the efficacy of two different social cognitive interventions.

Noradrenergic Suppression of Persistent Firing in Hippocampal CA1 Pyramidal Cells through cAMP-PKA Pathway.

Persistent firing is believed to be a cellular correlate of working memory. While the effects of noradrenaline (NA) on working memory have widely been described, its effect on the cellular mechanisms of persistent firing remains largely unknown. Using intracellular recordings, we demonstrate that persistent firing is supported by individual neurons in hippocampal CA1 pyramidal cells through cholinergic receptor activation, but is dramatically attenuated by NA.

Contribution of KCNQ and TREK Channels to the Resting Membrane Potential in Sympathetic Neurons at Physiological Temperature.

The ionic mechanisms controlling the resting membrane potential (RMP) in superior cervical ganglion (SCG) neurons have been widely studied and the M-current (I, KCNQ) is one of the key players. Recently, with the discovery of the presence of functional TREK-2 (TWIK-related K channel 2) channels in SCG neurons, another potential main contributor for setting the value of the resting membrane potential has appeared. In the present work, we quantified the contribution of TREK-2 channels to the resting membrane potential at physiological temperature and studied its role in excitability using patch-clamp techniques.

Involvement of TRPC4 and 5 Channels in Persistent Firing in Hippocampal CA1 Pyramidal Cells.

Persistent neural activity has been observed in vivo during working memory tasks, and supports short-term (up to tens of seconds) retention of information. While synaptic and intrinsic cellular mechanisms of persistent firing have been proposed, underlying cellular mechanisms are not yet fully understood. In vitro experiments have shown that individual neurons in the hippocampus and other working memory related areas support persistent firing through intrinsic cellular mechanisms that involve the transient receptor potential canonical (TRPC) channels.

PIP Mediated Inhibition of TREK Potassium Currents by Bradykinin in Mouse Sympathetic Neurons.

Bradykinin (BK), a hormone inducing pain and inflammation, is known to inhibit potassium M-currents (I) and to increase the excitability of the superior cervical ganglion (SCG) neurons by activating the Ca-calmodulin pathway. M-current is also reduced by muscarinic agonists through the depletion of membrane phosphatidylinositol 4,5-biphosphate (PIP). Similarly, the activation of muscarinic receptors inhibits the current through two-pore domain potassium channels (K2P) of the "Tandem of pore-domains in a Weakly Inward rectifying K channel (TWIK)-related channels" (TREK) subfamily by reducing PIP in mouse SCG neurons (mSCG).

SGK1.1 Reduces Kainic Acid-Induced Seizure Severity and Leads to Rapid Termination of Seizures.

Approaches to control epilepsy, one of the most important idiopathic brain disorders, are of great importance for public health. We have previously shown that in sympathetic neurons the neuronal isoform of the serum and glucocorticoid-regulated kinase (SGK1.1) increases the M-current, a well-known target for seizure control.

Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons.

Two-pore domain potassium channels (K2P) constitute major candidates for the regulation of background potassium currents in mammalian cells. Channels of the TREK subfamily are also well positioned to play an important role in sensory transduction due to their sensitivity to a large number of physiological and physical stimuli (pH, mechanical, temperature). Following our previous report describing the molecular expression of different K2P channels in the vagal sensory system, here we confirm that TREK channels are functionally expressed in neurons from the mouse nodose ganglion (mNG).

Do TRPC channels support working memory? Comparing modulations of TRPC channels and working memory through G-protein coupled receptors and neuromodulators.

Working memory is a crucial ability we use in daily life. However, the cellular mechanisms supporting working memory still remain largely unclear. A key component of working memory is persistent neural firing which is believed to serve short-term (hundreds of milliseconds up to tens of seconds) maintenance of necessary information.

Muscarinic modulation of TREK currents in mouse sympathetic superior cervical ganglion neurons.

Muscarinic receptors play a key role in the control of neurotransmission in the autonomic ganglia, which has mainly been ascribed to the regulation of potassium M-currents and voltage-dependent calcium currents. Muscarinic agonists provoke depolarization of the membrane potential and a reduction in spike frequency adaptation in postganglionic neurons, effects that may be explained by M-current inhibition. Here, we report the presence of a riluzole-activated current (IRIL ) that flows through the TREK-2 channels, and that is also inhibited by muscarinic agonists in neurons of the mouse superior cervical ganglion (mSCG).

Cholinergic receptor activation supports persistent firing in layer III neurons in the medial entorhinal cortex.

Medial temporal lobe (MTL) areas are crucial for memory tasks such as spatial working memory and temporal association memory, which require an active maintenance of memory for a short period of time (a few hundred milliseconds to tens of seconds). Recent work has shown that the projection from layer III neurons in the medial entorhinal cortex (MEC) to hippocampal region CA1, the temporoammonic (TA) pathway, might be specially important for these memory tasks. In addition, lesions to the entorhinal cortex disrupt persistent firing in CA1 which is believed to support active maintenance of memory.

Lidocaine effects on acetylcholine-elicited currents from mouse superior cervical ganglion neurons.

Lidocaine is a commonly used local anaesthetic that, besides blocking voltage-dependent Na(+) channels, has multiple inhibitory effects on muscle-type nicotinic acetylcholine (ACh) receptors (nAChRs). In the present study, we have investigated the effects of lidocaine on ACh-elicited currents (IAChs) from cultured mouse superior cervical ganglion (SCG) neurons, which mainly express heteromeric α3β4 nAChRs. Neurons were voltage-clamped by using the perforated-patch method and IAChs were elicited by fast application of ACh (100-300μM), either alone or in presence of lidocaine at different concentrations.

Expression of K2P channels in sensory and motor neurons of the autonomic nervous system.

Several types of neurons within the central and peripheral somatic nervous system express two-pore-domain potassium (K2P) channels, providing them with resting potassium conductances. We demonstrate that these channels are also expressed in the autonomic nervous system where they might be important modulators of neuronal excitability. We observed strong mRNA expression of members of the TRESK and TREK subfamilies in both the mouse superior cervical ganglion (mSCG) and the mouse nodose ganglion (mNG).

TRP channels and neural persistent activity.

One of the integrative properties of the nervous system is its capability to, by transient motor commands or brief sensory stimuli, evoke persistent neuronal changes, mainly as a sustained, tonic action potential firing. This neural activity, named persistent activity, is found in a good number of brain regions and is thought to be a neural substrate for short-term storage and accumulation of sensory or motor information [1]. Examples of this persistent neural activity have been reported in prefrontal [2] and entorhinal [3] cortices, as part of the neural mechanisms involved in short-term working memory [4].

Activation of TREK currents by the neuroprotective agent riluzole in mouse sympathetic neurons.

Background K2P channels play a key role in stabilizing the resting membrane potential, thereby modulating cell excitability in the central and peripheral somatic nervous system. Whole-cell experiments revealed a riluzole-activated current (I(RIL)), transported by potassium, in mouse superior cervical ganglion (mSCG) neurons. The activation of this current by riluzole, linoleic acid, membrane stretch, and internal acidification, its open rectification and insensitivity to most classic potassium channel blockers, indicated that I(RIL) flows through channels of the TREK [two-pore domain weak inwardly rectifying K channel (TWIK)-related K channel] subfamily.

TRPC channels underlie cholinergic plateau potentials and persistent activity in entorhinal cortex.

Persistent neuronal activity lasting seconds to minutes has been proposed to allow for the transient storage of memory traces in entorhinal cortex and thus could play a major role in working memory. Nonsynaptic plateau potentials induced by acetylcholine account for persistent firing in many cortical and subcortical structures. The expression of these intrinsic properties in cortical neurons involves the recruitment of a non-selective cation conductance.

Decrease of marine toxin content in bivalves by industrial processes.

Harmful algal blooms cause important economical losses due to the accumulation of toxins in shellfish. Natural detoxification occurs but this mechanism is very slow in most cases. The achievement of a method for the rapid detoxification of commercial bivalves would be very interesting for the shellfish harvesting sector in order to diminish economical losses due to harvesting areas closure.

A riluzole- and valproate-sensitive persistent sodium current contributes to the resting membrane potential and increases the excitability of sympathetic neurones.

Non-adapting superior cervical ganglion (SCG) neurones with a clustering activity and sub-threshold membrane potential oscillations were occasionally recorded, suggesting the presence of a persistent sodium current (I(NaP)). The perforated-patch technique was used to establish its properties and physiological role. Voltage-clamp experiments demonstrated that all SCG cells have a TTX-sensitive I(NaP) activating at about -60 mV and with half-maximal activation at about -40 mV.

Lipophilic toxins analyzed by liquid chromatography-mass spectrometry and comparison with mouse bioassay in fresh, frozen, and processed molluscs.

The search for alternative methods to the mouse bioassay (MBA) has intensified over recent years. The present work analyzes seven different species of shellfish (clams, small scallops, small clams, mussels, oysters, cockles, and edible whelks) in fresh, frozen boiled, and canned presentations using liquid chromatography-mass spectrometry (LC-MS/MS), and the results are compared with the same samples analyzed through MBA. The toxins studied were OA, DTX1, DTX2, YTX, PTX2, and AZA1, which are legislated in the EU, and SPX1, which is not regulated yet.

Characteristics of palytoxin-induced cytotoxicity in neuroblastoma cells.

Cation fluxes appear to play a key role in palytoxin-induced signal. There are other cellular targets that have not been described as well as the biochemical signaling cascades that transmit palytoxin-stimulated signals remain to be clarified. Since modifications of cations, mainly calcium, are generally associated to cell death or apoptosis, we wanted to further evaluate the effect of palytoxin on cell death.

Development of cholinergic modulation and graded persistent activity in layer v of medial entorhinal cortex.

During muscarinic modulation, principal neurons from layer V of rat medial entorhinal cortex (mEC) respond to repeated applications of a brief stimulus with a graded change in persistent firing frequency. This pattern of discharge has been proposed to represent an intrinsic mechanism for short-term memory operations. To investigate the implementation of persistent activity in mEC during development, we characterized the electrophysiological properties of layer V principal neurons in the mEC over a range of postnatal stages.

Spontaneous bursting and rhythmic activity in the cuneate nucleus of anaesthetized rats.

Spontaneous and rhythmic neuronal activity in dorsal column nuclei has long been identified in anesthetized cats. Here, we have studied the spontaneous behavior of cuneate cells in anesthetized rats through extracellular recording, showing that most cuneate neurones recorded (155 of 185) fired spontaneously. Overall, 74% of these spontaneously firing neurones were single-spiking and 26% were bursting.