Abstract The clearance of extracellular glutamate is mainly mediated by pH‐ and sodium‐dependent transport into astrocytes. During hepatic encephalopathy (HE), however, elevated concentrations are observed. primary candidate responsible for the toxic effects observed during HE ammonium (NH 4 + /NH 3 ). Here, we examined NH on steady‐state intracellular pH (pH i ) sodium concentration ([Na ] in cultured astrocytes two different age groups. Moreover, assessed influence transporter activity...

Ammonium (NH(4) (+) ) is required to maintain pathways involved in shuttling metabolic precursors between astrocytes and neurones. Under hyperammonaemic conditions, increases the cellular influx of NH(4) , accompanying changes ion concentrations, may contribute disruptions metabolism neurotransmission. We investigated mechanisms hippocampal slices by measuring acute /NH(3) -evoked intracellular pH (pH(i) sodium ([Na(+) ](i) ). In both neurones, application 5 mM Cl for 30-45 min decreased...

Memory deficits are a debilitating symptom of epilepsy, but little is known about mechanisms underlying cognitive deficits. Here, we describe Na+ channel-dependent mechanism altered hippocampal dendritic integration, degraded place coding and in spatial memory. Two-photon glutamate uncaging experiments revealed marked increase the fraction first-order CA1 pyramidal cell dendrites capable generating spikes kainate model chronic epilepsy. Moreover, epileptic mice were generated with lower...

The synapses formed by the mossy fiber (MF) axons of hippocampal dentate gyrus granule neurons onto CA3 pyramidal exhibit an intriguing form experience-dependent synaptic plasticity that is induced and expressed presynaptically. In contrast to most other CNS synapses, long-term potentiation (LTP) at MF–CA3 synapse readily even during blockade postsynaptic glutamate receptors. Furthermore, blocking voltage-gated Ca 2+ channels prevents MF-LTP, supporting involvement presynaptic signaling via...

Feedback inhibitory motifs are thought to be important for pattern separation across species. How feedback circuits may implement of biologically plausible, temporally structured input in mammals is, however, poorly understood. We have quantitatively determined key properties netfeedback inhibition the mouse dentate gyrus, a region critically involved separation. is recruited steeply with low dynamic range (0% 4% active GCs), and non-uniform spatial profile. Additionally, net shows...

Summary Objective The maturation of adult‐born granule cells and their functional integration into the network is thought to play a key role in proper functioning dentate gyrus. In temporal lobe epilepsy, gyrus develop abnormally possess hilar basal dendrite (HBD). Although morphological studies have shown that these HBDs synapses, little known about properties or intrinsic aberrant dendrites. Methods We performed patch‐clamp recordings within cell layer “normotopic” from sham‐control status...

Dendritic voltage-gated ion channels profoundly shape the integrative properties of neuronal dendrites. In epilepsy, numerous changes in dendritic have been described, all them due to either their altered transcription or phosphorylation. pilocarpine-treated chronically epileptic rats, we describe a novel mechanism that causes an increased proximal persistent Na + current ( I NaP ). We demonstrate using combination electrophysiology and molecular approaches upregulation is relief from...

The contributions of HCO 3 − ‐dependent, DIDS‐sensitive mechanisms to the maintenance steady‐state pH i , and regulation their activities by cAMP‐dependent protein kinase (PKA), were investigated in CA1 neurons with H + ‐sensitive fluorophore, BCECF. addition /CO 2 ‘low’ (pH ≤ 7.20) ‘high’ > initial values under Hepes‐buffered conditions, increased decreased respectively. Conversely, ‐buffered DIDS caused decrease increase low high values, In presence, but not absence, PKA inhibitor...

Genetically encoded calcium indicators (GECIs) such as GCaMP are invaluable tools in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used target expression specific brain regions, can be conveniently with any mouse strain interest without the need for prior crossing a GECI line and avoids potential hazards due chronic during development. A key requirement monitoring an indicator that itself minimally affects activity. Here, common...

Genetically encoded calcium indicators (GECIs) such as GCaMP are invaluable tools in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used target expression specific brain regions, can be conveniently with any mouse strain interest without the need for prior crossing a GECI line, and avoids potential hazards due chronic during development. A key requirement monitoring an indicator that itself minimally affects activity. Here, common...

Abstract Cellular behavior is orchestrated by the complex interactions of a myriad intracellular signal transduction pathways. To understand and investigate role individual components in such signaling networks, availability specific inhibitors paramount importance. We report generation validation novel variant an RNA aptamer that selectively inhibits mitogen‐activated kinase pathway neurons. demonstrate retains function under conditions application through patch‐clamp pipette efficiently...

The size and structure of the dendritic arbor play important roles in determining how synaptic inputs neurons are converted to action potential output. regulatory mechanisms governing development dendrites, however, insufficiently understood. evolutionary conserved Ste20/Hippo kinase pathway has been proposed an role regulating formation maintenance architecture. A key element this pathway, Ste20-like (SLK), regulates cytoskeletal dynamics non-neuronal cells is strongly expressed throughout...

Abstract Cellular behavior is orchestrated by the complex interactions of a myriad intracellular signal transduction pathways. To understand and investigate role individual components in such signaling networks, availability specific inhibitors paramount importance. We report generation validation novel variant an RNA aptamer that selectively inhibits mitogen‐activated kinase pathway neurons. demonstrate retains function under conditions application through patch‐clamp pipette efficiently...

The Ca(2+)-dependent slow afterhyperpolarization (AHP) is an important determinant of neuronal excitability. Although it established that modest changes in extracellular pH (pH(o)) modulate the AHP, relative contributions priming Ca(2+) signal and intracellular (pH(i)) to this effect remain poorly defined. To gain a better understanding modulation AHP by pH(o), we performed simultaneous recordings free calcium concentration ([Ca(2+)](i)), pH(i), cultured rat hippocampal neurons coloaded with...

We examined the effects of changes in pH(o) and pH(i) on currents contributing to medium slow afterhyperpolarizations (mI(AHP) sI(AHP), respectively) rat CA1 neurones. Reducing from 7.4 6.7 inhibited mI(AHP) sI(AHP) whereas increasing 7.7 augmented and, a greater extent, sI(AHP). The ability modulate reflected Ca(2+)-activated K(+) current, I(AHP), Co(2+)- XE991-resistant component mI(AHP), but not muscarine-sensitive I(M). In presence 1 microM TTX 5 mM TEA, low pH(o)-evoked reductions were...

Genetically encoded calcium indicators (GECIs) such as GCaMP are an invaluable tool in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used target expression specific brain regions, can be conveniently with any mouse strain interest without the need for prior crossing a GECI line and avoids potential hazards due chronic during development. A key requirement monitoring indicator that itself minimally affects activity. Here, common...

Genetically encoded calcium indicators (GECIs) such as GCaMP are invaluable tools in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used target expression specific brain regions, can be conveniently with any mouse strain interest without the need for prior crossing a GECI line, and avoids potential hazards due chronic during development. A key requirement monitoring an indicator that itself minimally affects activity. Here, common...

Abstract Hepatic encephalopathy (HE) is a neuropsy­chiatric disorder associated with acute and chronic liver failure. Ammonium the most likely toxin responsible for observed neu­rological deficits, reaching 5 mM in CNS during HE. Additionally, ammonium preferentially affects astrocytes. Conversion of glutamate to glutamine, occurring exclu­sively astrocytes, sole pathway detoxification, while glutamine increases astrocytes Further­more, elevated extracellular con­centrations, commonly HE...

Zusammenfassung Hepatische Enzephalopathie (HE) ist eine signifikante Begleiterscheinung akuter und chronischer Lebererkrankungen, die durch Vielzahl unterschiedlicher Funktionsstörungen des Gehirns gekennzeichnet ist. Als Hauptursache gilt ein Anstieg der Ammoniumionenkonzentration, wobei HE primär als Gliafunktions­störung angesehen wird. Ammonium wird das Enzym Glutaminsynthetase in Astrozyten mit Glutamat zu Glutamin fixiert weisen bei einen starken ihres Glutamingehalts auf, während...