Regulation of hippocampal synaptic plasticity thresholds and changes in exploratory and learning behavior in dominant negative NPR-B mutant rats

The second messenger cyclic GMP affects synaptic transmission and modulates synaptic plasticity and certain types of learning and memory processes. The impact of the natriuretic peptide receptor B (NPR-B) and its ligand C-type natriuretic peptide (CNP), one of several cGMP producing signaling systems, on hippocampal synaptic plasticity and learning is, however, less well understood. We have previously shown that the NPR-B ligand CNP increases the magnitude of long-term depression (LTD) in hippocampal area CA1, while reducing the induction of long-term potentiation (LTP). We have extended this line of research to show that bidirectional plasticity is affected in the opposite way in rats expressing a dominant-negative mutant of NPR-B (NSE-NPR- BΔKC) lacking the intracellular guanylyl cyclase domain under control of a promoter for neuron-specific enolase. The brain cells of these transgenic rats express functional dimers of the NPR-B receptor containing the dominant- negative NPR-BΔKC mutant, and therefore show decreased CNP-stimulated cGMP- production in brain membranes. The NPR-B transgenic rats display enhanced LTP but reduced LTD in hippocampal slices. When the frequency-dependence of synaptic modification to afferent stimulation in the range of 1–100 Hz was assessed in transgenic rats, the threshold for both, LTP and LTD induction, was shifted to lower frequencies. In parallel, NPR-BΔKC rats exhibited an enhancement in exploratory and learning behavior. These results indicate that bidirectional plasticity and learning and memory mechanism are affected in transgenic rats expressing a dominant-negative mutant of NPR-B. Our data substantiate the hypothesis that NPR-B-dependent cGMP signaling has a modulatory role for synaptic information storage and learning

GABAA receptor subtype involvement in addictive behaviour

GABAA receptors form the major class of inhibitory neurotransmitter receptors in the mammalian brain. This review sets out to summarise the evidence that variations in genes encoding GABAA receptor isoforms are associated with aspects of addictive behaviour in humans, while animal models of addictive behaviour also implicate certain subtypes of GABAA receptor. In addition to outlining the evidence for the involvement of specific subtypes in addiction, we summarise the particular contributions of these isoforms in control over the functioning of brain circuits, especially the mesolimbic system, and make a first attempt to bring together evidence from several fields to understanding potential involvement of GABAA Receptor Subtypes in addictive behaviour. While the weight of the published literature is on alcohol dependency, the underlying principles outlined are relevant across a number of different aspects of addictive behaviour

Läsionsinduzierte Änderungen der intrazellulären Kalziumkonzentration und der LTP von Neuronen im visuellen Kortex der Ratte

In der vorliegenden Arbeit wird das räumlich-zeitliche Muster funktioneller Änderungen in der Umgebung von kortikalen Läsionen beschrieben und seine mögliche Auswirkung auf die Neuordnung und Plastizität nach Läsion diskutiert. Kalzium-Imaging von Neuronen in Schicht II/III zeigte eine erhöhte [Ca$^{2+}$]$_{IR}$ und einen vergrößerten Kalziumeinstrom, die am auffallendsten in den ersten 6 Tagen nach der Operation in Entfernungen von 3-4 mm lateral vom Läsionsrand waren. Diese Zunahme in [Ca$^{2+}$]$_{I}$ war D-AP5 und GYKI abhängig, d. h. NMDA- und AMPA-Rezeptoren waren für diesen Effekt verantwortlich. Die erhöhte LTP nach der Läsion sowie der erhöhte Kalziumeinstrom nach TBS sind zum Teil NMDA-Rezeptor abhängig. Das unterstützt die Hypothese, dass erhöhtes Kalzium für die Stärke der LTP verantwortlich ist und dass der erhöhte Kalziumeinstrom und die verstärkte LTP ein erster Schritt für die funktionellen Reorganisationsprozesse nach einer Läsion in visuellem Kortex sein können

KP: Differences between cation-chloride co-transporter functions in the visual cortex of pigmented and albino rats

Abstract Albinism in mammals is accompanied by specific morphological and functional alterations of the visual system. To understand their cellular basis we studied the physiological characteristics and transmembrane currents of pyramidal neurons in 350-lm-thick slices of visual cortex from pigmented and albino rats using whole-cell and gramicidin perforated patch-clamp recordings. The resting membrane potential was significantly more positive and the rheobase was significantly lower in neurons of layers II ⁄ III and V in albinos as compared with pigmented rats. No significant differences were found in the input resistance, time constant and chronaxy. Whereas the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated currents were not significantly different, the maximum c-aminobutyric acid (GABA) A receptor (GABA A R)-mediated currents and miniature inhibitory postsynaptic currents showed significantly lower amplitudes in neurons of layer V in visual cortex of albinos as compared with pigmented rats. The reversal potential of the GABA A R-mediated currents (E GABA ) was significantly shifted to more positive values in albinos. Pharmacological experiments showed that this shift could be caused by an increased action of the inward chloride co-transporter NKCC1 and reduced action of the outward chloride co-transporter KCC2 in albino rats. This difference seems to be restricted to the visual cortex because in pyramidal neurons from frontal cortex E GABA was not significantly different in albinos as compared with pigmented rats. These results are discussed in relation to functional alterations in the albino visual system