Multiple long-range projections convey position information to the agranular retrosplenial cortex.

Neuronal signals encoding the animal's position widely modulate neocortical processing. While these signals are assumed to depend on hippocampal output, their origin has not been investigated directly. Here, we asked which brain region sends position information to the retrosplenial cortex (RSC), a key circuit for memory and navigation.

Different pH-sensitivity patterns of 30 sodium channel inhibitors suggest chemically different pools along the access pathway.

The major drug binding site of sodium channels is inaccessible from the extracellular side, drug molecules can only access it either from the membrane phase, or from the intracellular aqueous phase. For this reason, ligand-membrane interactions are as important determinants of inhibitor properties, as ligand-protein interactions. One-way to probe this is to modify the pH of the extracellular fluid, which alters the ratio of charged vs.

Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals.

The release of GABA from cholecystokinin-containing interneurons is modulated by type-1 cannabinoid receptors (CB1). Here we tested the hypothesis that the strength of CB1-mediated modulation of GABA release is related to the CB1 content of axon terminals. Basket cell boutons have on average 78% higher CB1 content than those of dendritic-layer-innervating (DLI) cells, a consequence of larger bouton surface and higher CB1 density.

Presynaptic calcium channel inhibition underlies CB₁ cannabinoid receptor-mediated suppression of GABA release.

CB1 cannabinoid receptors (CB1) are located at axon terminals and effectively control synaptic communication and thereby circuit operation widespread in the CNS. Although it is partially uncovered how CB1 activation leads to the reduction of synaptic excitation, the mechanisms of the decrease of GABA release upon activation of these cannabinoid receptors remain elusive. To determine the mechanisms underlying the suppression of synaptic transmission by CB1 at GABAergic synapses, we recorded unitary IPSCs (uIPSCs) at cholecystokinin-expressing interneuron-pyramidal cell connections and imaged presynaptic [Ca(2+)] transients in mouse hippocampal slices.

GluN2B-containing NMDA receptors as possible targets for the neuroprotective and antidepressant effects of fluoxetine.

Accumulating evidence has indicated the involvement of glutamatergic neurotransmission in the pathophysiology of excitotoxicity and in the mechanism of action of antidepressants. We have previously shown that tricyclic desipramine and the selective serotonin reuptake inhibitor fluoxetine inhibit NMDA receptors (NMDARs) in the clinically relevant, low micromolar concentration range. As the different subtypes of NMDARs are markedly different in their physiological and pathological functions, our aim was to investigate whether the effect of antidepressants is subtype-specific.

Classification of drugs based on properties of sodium channel inhibition: a comparative automated patch-clamp study.

Background: There is only one established drug binding site on sodium channels. However, drug binding of sodium channels shows extreme promiscuity: ∼25% of investigated drugs have been found to potently inhibit sodium channels. The structural diversity of these molecules suggests that they may not share the binding site, and/or the mode of action.

Fast- or slow-inactivated state preference of Na+ channel inhibitors: a simulation and experimental study.

Sodium channels are one of the most intensively studied drug targets. Sodium channel inhibitors (e.g.

Converging effects of Ginkgo biloba extract at the level of transmitter release, NMDA and sodium currents and dendritic spikes.

In this study, an attempt was made to integrate the effects of GINKGO BILOBA extract (GBE) in different experimental systems (IN VITRO cochlea, brain slice preparations and cortical cell culture) to elucidate whether these processes converge to promote neuroprotection or interfere with normal neural function. GBE increased the release of dopamine in the cochlea. NMDA-evoked currents were dose-dependently inhibited by rapid GBE application in cultured cortical cells.