<em>In Vivo</em> Electrophysiological Measurements on Mouse Sciatic Nerves

Electrophysiological studies allow a rational classification of various neuromuscular diseases and are of help, together with neuropathological ...

Friedrich Schiller University Jena

The mammalian hippocampus is certainly one of the best investigated brain regions. It fascinates neuroscientists particularly because of its important role in memory. The names for the various parts of the hippocampal formation were created in the course of the first thorough explorations of human brain anatomy. The present, internationally agreed terminology reflects an unfortunate muddle that has been going on for several hundred years. Not surprisingly, even today the origins of some of the names are not always given correctly. It is generally accepted that the Italian anatomist Arantius was the first to apply the term 'hippocampus' to part of that region in the human brain. To later authors, however, this name appeared more or less enigmatic and they proposed various other terms. Yet careful reading of the entire original text of Arantius leads to the conclusion that it was not the hippocampus in our modern terms but the dentate gyrus which he compared to a little sea horse or a silkworm.

Hippocampal terminology: concepts, misconceptions, origins.

Influx of Ca(2+) and Na(+) ions during an action potential can strongly affect the repolarization and the fast afterhyperpolarization (fAHP) if a neuron expresses Ca(2+)- and Na(+)-dependent K(+) currents (K(Ca) and K(Na)). This applies to cockroach abdominal dorsal unpaired median neurons (DUMs). Here the rapid activation of K(Ca) depends mainly on the P/Q-type Ca(2+) current. Adipokinetic hormones (AKHs)-insect counterparts to mammalian glucagon-mobilize energy reserves but also modulate neuronal activity and lead to enhanced locomotor activity. Cockroach AKH I accelerates spiking and enhances the fAHP of octopaminergic DUM neurons, and it is generally held that enhanced release of the biogenic amine from these and other neurons may lead to general arousal. AKH I modulates the voltage-gated Na(+) and P/Q-type Ca(2+) current and the background Ca(2+) current. Upregulation of P/Q-type Ca(2+) current increases the K(Ca) current, whereas enhanced inactivation of Na(+) current decreases the K(Na) current. We quantified the hormone-induced changes in ion currents in terms of Hodgkin-Huxley models and simulated the resulting activity of DUM neurons. Upregulation of P/Q-type Ca(2+) and K(Ca) current enhanced the hyperpolarization but had a weak effect on spiking. Downregulation of Na(+) and K(Na) current decreased hyperpolarization and slightly accelerated spiking. Superposition of these modulations produced an increase in fAHP while the spike frequency remained unchanged. Only when the upregulation of the pacemaking Ca(2+) background current was included in the simulated modulation the model reproduced the experimentally observed AKH-I-induced changes. The possible physiological relevance of this dual effect is discussed in respect to transmitter release and synaptic integration.

Peptidergic counter-regulation of Ca(2+)- and Na(+)-dependent K(+) currents modulates the shape of action potentials in neurosecretory insect neurons.

TipE is an auxiliary subunit of the Drosophila Para sodium channel. Here we describe four sequences, TEH1-4, homologous to TipE in the Drosophila melanogaster genome, harboring all typical structures of both TipE and the beta-Subunit family of big-conductance Ca(2+)-activated potassium channels: short cytosolic N- and C-terminal stretches, two transmembrane domains, and a large extracellular loop with two disulfide bonds. Whereas TEH1 and TEH2 lack the TipE-specific extension in the extracellular loop, both TEH3 and TEH4 possess two extracellular EGF-like domains. A CNS-specific expression was found for TEH1, while TEH2-4 were more widely expressed. The genes for TEH2-4 are localized close to the tipE gene on chromosome 3L. Coexpression of TEH subunits with Para in Xenopus oocytes showed a strong (30-fold, TEH1), medium (5- to 10-fold, TEH2 and TEH3), or no (TEH4) increase in sodium current amplitude, while TipE increased the current 20-fold. In addition, steady-state inactivation and the recovery from fast inactivation were altered by coexpression of Para with TEH1. We conclude that members of the TEH-family are auxiliary subunits for Para sodium channels and possibly other ion channels.

Four novel sequences in Drosophila melanogaster homologous to the auxiliary Para sodium channel subunit TipE.

A chloride current, I(Cl,H), slowly activating on hyperpolarisation was investigated in Drosophila melanogaster larval muscles using the two-electrode voltage clamp. Sizeable currents were observed after the intracellular chloride concentration ([Cl-]i) had been elevated by diffusion of Cl- from the electrodes. The time course of I(Cl,H) was rather variable and required two exponentials to be accurately described. The reversal potential, -40 to -20 mV in Cl- -loaded fires, shifted on lowering external [Cl-] in the positive direction. Steady-state activation of I(Cl,H) was characterised by V0.5 of approximately -120 mV and a slope factor, k, of approximately 10 mV at a [Cl-]i approximately 35 mmol l(-1). Raising [Cl-]i to approximately 50 mmol l(-1) caused a negative shift of V0.5 equivalent to the change of E(Cl) and led to a nearly threefold increase in maximal steady-state conductance. I(Cl,H) was resistant to 10 mmol l(-1) Zn2+ and 1 mmol l(-1) Cd2+ but was greatly reduced by 1 mmol l(-1) 9-anthracenecarboxylic acid (9-AC). I(Cl,H) was affected by changes of extracellular pH and increased on lowering extracellular osmolality. 9-AC also decreased muscle fibre resting conductance by approximately 20% and increased muscle contractions. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis confirmed the expression of all three ClC genes in muscle, and immunohistochemistry indicated location of Drosophila melanogaster chloride channel-2 (DmClC-2) at the Z-lines. We conclude that DmClC-2 accounts for the channels underlying I(Cl,H), and in part for the resting chloride conductance. DmClC-2 may serve general homeostatic mechanisms such as pH- and osmo-regulation or may support muscle function on high motor activity or during a particular neurohormonal state of the animal.

Properties and possible function of a hyperpolarisation-activated chloride current in Drosophila.

Adaptation influences perception not only of simple stimulus qualities such as motion or colour, but also of complex stimuli such as faces. Here we demonstrate contrasting aftereffects of adaptation to facial age. In Experiment 1, participants adapted to either young or old faces, and subsequently estimated the age of morphed test faces with interpolated ages of 30, 40, 50 or 60 years. Following adaptation to old adaptors, test faces were classified as much younger when compared to classifications of the same test faces following adaptation to young faces, which in turn caused subjective test face "aging". These aftereffects were reduced but remained clear even when facial gender changed between adaptor and test faces. In Experiment 2, we induced simultaneous opposite age aftereffects for female and male faces. Overall, these results demonstrate interactions in the perception of facial age and gender, and support dissociable neuronal coding of male and female faces.

Young without plastic surgery: perceptual adaptation to the age of female and male faces.

Apart from speech content, the human voice also carries paralinguistic information about speaker identity. Voice identification and its neural correlates have received little scientific attention up to now. Here we use event-related potentials (ERPs) in an adaptation paradigm, in order to investigate the neural representation and the time course of vocal identity processing. Participants adapted to repeated utterances of vowel-consonant-vowel (VCV) of one personally familiar speaker (either A or B), before classifying a subsequent test voice varying on an identity continuum between these two speakers. Following adaptation to speaker A, test voices were more likely perceived as speaker B and vice versa, and these contrastive voice identity aftereffects (VIAEs) were much more pronounced when the same syllable, rather than a different syllable, was used as adaptor. Adaptation induced amplitude reductions of the frontocentral N1-P2 complex and a prominent reduction of the parietal P3 component, for test voices preceded by identity-corresponding adaptors. Importantly, only the P3 modulation remained clear for across-syllable combinations of adaptor and test stimuli. Our results suggest that voice identity is contrastively processed by specialized neurons in auditory cortex within ∼250 ms after stimulus onset, with identity processing becoming less dependent on speech content after ∼300 ms.

Neural correlates of adaptation to voice identity.

Priming (PR) and adaptation-related aftereffects (AEs) are two phenomena when recent perceptual experiences alter face perception. While AEs are often reflected in contrastive perceptual biases, PR typically leads to behavioural facilitation. Previous research suggests that both phenomena modulate broadly similar components of the event-related potentials (ERPs). To disentangle the underlying neural mechanisms of PR and AE, we induced both effects within the same subjects and paradigm. We presented pairs of stimuli, where the first (S1) was a famous face (identity A, B or C), a morph between two famous faces (50/50% A/B), or a Fourier phase randomized face (as a control stimulus matched for low-level visual information) and the second (S2) was a face drawn from morph continua between identity A and B. Participants' performance in matching S2s to either A or B revealed contrastive aftereffects for ambiguous S2 faces, which were more likely perceived as identity B following the presentation of A and vice versa. Unambiguous S2 faces, however, showed PR, with significantly shorter response times, as well as higher classification performance, for identity-congruent than for incongruent S1-S2 pairs. Analyses of the simultaneously recorded ERPs revealed clear categorical adaptation at around 155-205 msec post-stimulus onset. We also found amplitude modulations for unambiguous S2 faces following identity-congruent S1 faces, related to PR, starting at 90 msec and being the most pronounced at around 205-255 msec. For ambiguous S2 faces, we also observed an ERP effect at around 205-255 msec that was correlated with behavioural AEs. Our results show that face PR and AEs are present simultaneously within a single paradigm, depending on the ambiguity of S2 faces and/or on the similarity of S1 and S2, and suggest that exclusive mechanisms might underlie both PR and AEs and that object-category and identity processing might run in parallel during face processing.

Neural correlates of priming and adaptation in familiar face perception.

Quantized Liquid Density-Functional Theory (QLDFT) [S. Patchkovskii and T. Heine, Phys. Rev. E 80, 031603 (2009)], a method developed to assess the adsorption of gas molecules in porous nanomaterials, is reformulated within the grand canonical ensemble. With the grand potential it is possible to compare directly external and internal thermodynamic quantities. In our new implementation, the grand potential is minimized utilizing the Car-Parrinello approach and gives, in particular for low temperature simulations, a significant computational advantage over the original canonical approaches. The method is validated against original QLDFT, and applied to model potentials and graphite slit pores.

Grand-canonical quantized liquid density-functional theory in a Car-Parrinello implementation.

Adaptation-related aftereffects (AEs) show how face perception can be altered by recent perceptual experiences. Along with contrastive behavioural biases, modulations of the early event-related potentials (ERPs) were typically reported on categorical levels. Nevertheless, the role of the adaptor stimulus per se for face identity-specific AEs is not completely understood and was therefore investigated in the present study. Participants were adapted to faces (S1s) varying systematically on a morphing continuum between pairs of famous identities (identities A and B), or to Fourier phase-randomized faces, and had to match the subsequently presented ambiguous faces (S2s; 50/50% identity A/B) to one of the respective original faces. We found that S1s identical with or near to the original identities led to strong contrastive biases with more identity B responses following A adaptation and vice versa. In addition, the closer S1s were to the 50/50% S2 on the morphing continuum, the smaller the magnitude of the AE was. The relation between S1s and AE was, however, not linear. Additionally, stronger AEs were accompanied by faster reaction times. Analyses of the simultaneously recorded ERPs revealed categorical adaptation effects starting at 100 ms post-stimulus onset, that were most pronounced at around 125-240 ms for occipito-temporal sites over both hemispheres. S1-specific amplitude modulations were found at around 300-400 ms. Response-specific analyses of ERPs showed reduced voltages starting at around 125 ms when the S1 biased perception in a contrastive way as compared to when it did not. Our results suggest that face identity AEs do not only depend on physical differences between S1 and S2, but also on perceptual factors, such as the ambiguity of S1. Furthermore, short-term plasticity of face identity processing might work in parallel to object-category processing, and is reflected in the first 400 ms of the ERP.

Adaptor identity modulates adaptation effects in familiar face identification and their neural correlates.

The repetition of a given stimulus leads to the attenuation of the functional magnetic resonance imaging (fMRI) signal compared with unrepeated stimuli, a phenomenon called fMRI adaptation or repetition suppression (RS). Previous studies have related RS of the fMRI signal behaviorally both to improved performance for the repeated stimulus (priming) and to shifts of perception away from the first stimulus (adaptation-related aftereffects). Here we used identical task (sex discrimination), trial structure [stimulus 1 (S1): 3,000 ms, interstimulus interval: 600 ms, stimulus 2 (S2): 300 ms], and S2 stimuli (androgynous faces) to test how RS of the face-specific areas of the occipito-temporal cortex relates to priming and aftereffects. By varying S1, we could induce priming (significantly faster reaction times when S1 and S2 were identical compared with different images) as well as sex-specific aftereffect [an increased ratio of male responses if S1 was a female face compared with ambiguous faces or to Fourier-randomized noise (FOU) images]. Presenting any face as S1 led to significant RS of the blood oxygen level-dependent signal in the fusiform and occipital face areas as well as in the lateral occipital cortex of both hemispheres compared with FOU, reflecting stimulus category-specific encoding. Additionally, while sex-specific adaptation effects were only observed in occipital face areas, primed trials led to a signal reduction in both face-selective regions. Altogether, these results suggest the differential neural mechanisms of adaptation and repetition priming.

Christian Walther

Friedrich Schiller University Jena

In Vivo Electrophysiological Measurements on Mouse Sciatic Nerves