Biomedical subjects

T Hensch

Publications and source records attributed to T Hensch.

5 recordsLinked to original sources

PubMed2006

Serotonin transporter gene variation impacts innate fear processing: Acoustic startle response and emotional startle.

Anxiety-related behaviors are closely linked to neural circuits relaying fear-specific information to the amygdala. Many of these circuits, like those underlying processing of innate fear, are remarkably well understood. Recent imaging studies have contributed to this knowledge by discriminating more detailed corticoamygdalar associations mediating processing fear and anxiety. However, little is known about the underlying molecular mechanisms. We used the acoustic startle paradigm to investigate the impact of molecular genetic variation of serotonergic function on the acoustic startle response and its fear potentiation. Startle magnitudes to noise bursts as measured with the eye blink response were recorded in 66 healthy volunteers under four conditions: presenting unpleasant and pleasant affective pictures as well as neutral pictures, and presenting the startle stimulus without additional stimuli as a baseline. Subjects were genotyped for functional polymorphism in the transcriptional control region of the serotonin transporter gene (5-hydroxytryptamine transporter gene-linked region: 5-HTTLPR). Analyses of variance revealed a significant effect of 5-HTTLPR on overall startle responses across conditions. Carriers of the short (s) allele exhibited stronger startle responses than l/l homozygotes. However, we could not confirm our hypothesis of enhanced fear potentiation of the startle in s allele carriers. In conclusion, the results provide first evidence that the startle response is sensitive to genetic variation in the serotonin pathway. Despite some issues remaining to be resolved, the startle paradigm may provide a valuable endophenotype of fear processing and underlying serotonergic influences.

Acoustic Stimulation↗

PubMed2004

Specific GABA(A) circuits in brain development and therapy.

GABAergic interneurons are highly diverse and operate with a corresponding diversity of GABA(A) receptor subtypes in controlling behaviour. In this article, we review the significance of GABA(A) receptor heterogeneity for neural circuit development and central nervous system pharmacology. GABA(A) receptor subtypes were identified as selective targets for behavioural actions of benzodiazepines and of selected intravenous anesthetic agents using point mutations which render a specific receptor subtype insensitive to the action of the respective drugs and also by novel subtype-selective ligands. The pharmacological separation of anxiolysis and sedation guides the development of novel anxiolytics, while inverse agonism at extrasynaptic GABA(A) receptors involved in learning and memory is currently being evaluated as a novel therapeutic principle for symptomatic memory enhancement.

Anesthetics↗

PubMed1996

Calcium-induced long-term depression in the visual cortex of the rat in vitro.

1. In many brain areas, including neocortex and hippocampus, excitatory synapses can undergo both long-term potentiation (LTP) and long-term depression (LTD). It is established that a change in the postsynaptic calcium concentration ([Ca2+]i) is critical for the induction of both LTP and LTD. Protocols that induce these long-term synaptic modifications typically involve afferent stimulation. But, in hippocampus, LTP can also be induced by a transient increase of the extracellular calcium concentration ([Ca2+]o). The purpose of the present study was to determine whether raising [Ca2+]o also induces long-term modifications of excitatory synaptic transmission in the neocortex. 2. Intracellular recordings were obtained from regular spiking cells in layers II-III of slices of the rat visual cortex. Test stimuli were evoked with stimulation electrodes located in the white matter (w.m.) below the recorded cell and intracortically (i.c.) adjacent to the cell. Both the depolarizing slope and the amplitude of excitatory postsynaptic potentials (EPSPs) were measured. For exposure to elevated [Ca2+]o, the normal medium ([Ca2+]o = 2 mM) was exchanged for a period of 10 min against a medium containing 4 mM [Ca2+]o. 3. Elevated [Ca2+]o leads, after return to normal medium, to a long-lasting decrease of intracellularly recorded synaptic responses to both w.m. and i.c. stimulation even if activation of these two pathways is discontinued or N-methyl-D-aspartate (NMDA) receptors are blocked during elevated [Ca2+]o. This decrease is due to reduced efficacy of excitatory transmission because it is observed in the presence of the gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline. 4. Induction of LTD by raising [Ca2+]o is voltage dependent. First, elevated [Ca2+]o elicits LTD only in cells whose resting membrane potential (Vmr) is less polarized than -79 mV (and more polarized than -70 mV, which is the Vmr of the least polarized cell). Second, hyperpolarizing cells whose Vmr is in this susceptible range by 20 mV below Vmr during exposure to high [Ca2+]o prevents Ca2+-induced LTD. Third, when elevated [Ca2+]o is associated with postsynaptic depolarizing pulses, LTD is readily induced in cells whose Vmr is more polarized than -79 mV. This voltage dependence implies that the depression is induced by a postsynaptic process and hence that it occurs at synapses formed by excitatory terminals on the recorded neuron. 5. Assuming that a transient elevation of [Ca2+]o leads to an increase of [Ca2+]i, the results of this study suggest that a transient increase of [Ca2+]i is sufficient to elicit LTD. This may provide a mechanism for the induction of heterosynaptic LTD, a depression that occurs in afferents that are silent while the postsynaptic neuron is activated by other inputs.

Animals↗

PubMed1991

Differential blocking action of Joro spider toxin analog on parallel fiber and climbing fiber synapses in cerebellar Purkinje cells.

Synaptic potentials were recorded intracellularly from Purkinje cells in guinea pig cerebellar slices. EPSPs evoked by stimulation of parallel fibers were effectively blocked by perfusion of a slice with the synthetic analog of Joro spider toxin, 1-naphthylacetyl-spermine (NAS) at 250 microM. However, it did not influence those responses evoked by stimulation of climbing fibers. This action of NAS is in contrast to other commonly used glutamate antagonists, CNQX or APV: CNQX (5 microM) blocked both parallel fiber- and climbing fiber-induced responses, while APV (up to 1 mM) did not influence either except for a weak reduction observed in climbing fiber responses. NAS thus provides a useful tool for pharmacologically distinguishing parallel fiber and climbing fiber synapses.

2-Amino-5-phosphonovalerate↗

PubMed1991

The role of cerebellar flocculus in adaptive gain control of ocular reflexes.

Sustained oscillation of the head of an alert animal with inphase or outphase combination of screen oscillation in the horizontal plane induced marked adaptive changes in the gain of the horizontal vestibulo-ocular reflex (HVOR). These changes are assumed to be a prototype of motor learning by the cerebellar flocculus. Several lines of experimental evidence, using rabbits or monkeys as experimental material, have consistently suggested that the plastic changes of neuronal activities of a particular group of floccular Purkinje cells (H-cells) are the sources of the HVOR adaptation.

Adaptation, Physiological↗