Neural activity in human hippocampal formation reveals the spatial context of retrieved memories.

In many species, spatial navigation is supported by a network of place cells that exhibit increased firing whenever an animal is in a certain region of an environment. Does this neural representation of location form part of the spatiotemporal context into which episodic memories are encoded? We recorded medial temporal lobe neuronal activity as epilepsy patients performed a hybrid spatial and episodic memory task. We identified place-responsive cells active during virtual navigation and then asked whether the same cells activated during the subsequent recall of navigation-related memories without actual navigation. Place-responsive cell activity was reinstated during episodic memory retrieval. Neuronal firing during the retrieval of each memory was similar to the activity that represented the locations in the environment where the memory was initially encoded.

Safety of hybrid electrodes for single-neuron recordings in humans.

BACKGROUND: Intracranial in vivo recordings of individual neurons in humans are increasingly performed for a better understanding of the mechanisms of epileptogenesis and of the neurobiological basis of cognition. So far, information about the safety of stereotactic implantations and of magnetic resonance imaging (MRI) with hybrid depth electrodes is scarce. OBJECTIVE: The aim of this study was to assess neurosurgical safety of implantations, recordings, and imaging using hybrid electrodes in humans. METHODS: Perioperative and long-term safety of implantation of a total of 88 hybrid depth electrodes with integrated microwires was assessed retrospectively in 25 consecutive epilepsy patients who underwent implantation of electrodes from 2007 to 2011 based on electronically stored charts. Safety aspects of MRI are reported from both in vitro and in vivo investigations. Precision of electrode implantation is evaluated based on intraoperative computed tomography and pre- and postoperative MRI. RESULTS: There was no clinically relevant morbidity associated with the use of hybrid electrodes in any of the patients. Precision of recordings from the targets aimed at was similar to that of standard depth electrodes. In vitro studies demonstrated the absence of relevant heating of hybrid electrodes with newly designed connectors with MRI at 1.5 T, corresponding to well-tolerated clinical MRI in patients. CONCLUSION: Given the technical approach described here, precise targeting and safe use are possible with hybrid electrodes containing microwires for in vivo recording of human neuronal units.

Positive shifts of the GABAA receptor reversal potential due to altered chloride homeostasis is widespread after status epilepticus.

PURPOSE: γ-Aminobutyric acid (GABA)ergic transmission plays an important role in the initiation of epileptic activity and the generation of ictal discharges. The functional alterations in the epileptiform hippocampus critically depend on GABAergic mechanisms and cation-chloride cotransporters. METHODS: To understand the cellular basis of specific functional alterations in the epileptic hippocampus, we studied physiologic characteristics and pharmacologically isolated evoked GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) recorded from principal neurons in hippocampal slices from status epilepticus (SE) and control rats using whole-cell and gramicidin perforated patch-clamp recordings. KEY FINDINGS: Whereas the resting membrane potential and input resistance were not significantly different between control and epileptic tissue, the reversal potential (E(GABA) ) of IPSCs was significantly shifted to more positive values in SE rats with regard to the resting membrane potential. Pharmacologic experiments and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) showed that the observed changes in the epileptic tissue were due to a decreased ratio of the main Cl(-) extrusion transporter (K(+) -Cl(-) cotransporter, KCC2) to the main Cl(-) uptake transporter (Na(+) -K(+) -2Cl(-) cotransporter, NKCC1). SIGNIFICANCE: Our results suggest that alterations of cation-chloride cotransporter functions, comprising a higher NKCC1 action, contribute to hyperexcitability within the hippocampus following SE.

Asynchronous GABA release generates long-lasting inhibition at a hippocampal interneuron-principal neuron synapse.

Hippocampal GABAergic interneurons show diverse molecular and morphological properties. The functional significance of this diversity for information processing is poorly understood. Here we show that cholecystokinin (CCK)-expressing interneurons in rat dentate gyrus release GABA in a highly asynchronous manner, in contrast to parvalbumin (PV) interneurons. With a gamma-frequency burst of ten action potentials, the ratio of asynchronous to synchronous release is 3:1 in CCK interneurons but is 1:5 in parvalbumin interneurons. N-type channels trigger synchronous and asynchronous release in CCK interneuron synapses, whereas P/Q-type Ca(2+) channels mediate release at PV interneuron synapses. Effects of Ca(2+) chelators suggest that both a long-lasting presynaptic Ca(2+) transient and a large distance between Ca(2+) source and sensor of exocytosis contribute to the higher ratio of asynchronous to synchronous release in CCK interneuron synapses. Asynchronous release occurs at physiological temperature and with behaviorally relevant stimulation patterns, thus generating long-lasting inhibition in the brain.

Presynaptic short-term depression is maintained during regulation of transmitter release at a GABAergic synapse in rat hippocampus.

To examine possible interactions between fast depression and modulation of inhibitory synaptic transmission in the hippocampus, we recorded from pairs of synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus of rat brain slices at 34 degrees C. Multiple-pulse depression (MPD) was examined in trains of 5 or 10 inhibitory postsynaptic currents (IPSCs) evoked at frequencies of 10-100 Hz under several conditions that inhibit transmitter release: block of voltage-dependent Ca2+ channels by Cd2+ (10 microM), activation of gamma-amino-butyric acid type B receptors (GABA(B)Rs) by baclofen (10 microM) and activation of muscarinic acetylcholine receptors (mAchRs) by carbachol (2 microM). All manipulations led to a substantial inhibition of synaptic transmission, reducing the amplitude of the first IPSC in the train (IPSC1) by 72%, 61% and 29%, respectively. However, MPD was largely preserved under these conditions (0.34 in control versus 0.31, 0.50 and 0.47 in the respective conditions at 50 Hz). Similarly, a theta burst stimulation (TBS) protocol reduced IPSC1 by 54%, but left MPD unchanged (0.40 in control and 0.39 during TBS). Analysis of both fractions of transmission failures and coefficients of variation (CV) of IPSC peak amplitudes suggested that MPD had a presynaptic expression site, independent of release probability. In conclusion, different types of presynaptic modulation of inhibitory synaptic transmission converge on a reduction of synaptic strength, while short-term dynamics are largely unchanged.