Gytis Svirskis

Asymmetric excitatory synaptic dynamics underlie interaural time difference processing in the auditory system.

In order to localize sounds in the environment, the auditory system detects and encodes differences in signals between each ear. The exquisite sensitivity of auditory brain stem neurons to the differences in rise time of the excitation signals from the two ears allows for neuronal encoding of microsecond interaural time differences.

Subthreshold outward currents enhance temporal integration in auditory neurons

Abstract.Many auditory neurons possess low-threshold potassium currents (IKLT) that enhance their responsiveness to rapid and coincident inputs. We present recordings from gerbil medial superior olivary (MSO) neurons in vitro and modeling results that illustrate how IKLT improves the detection of brief signals, of weak signals in noise, and of the coincidence of signals (as needed for sound localization). We quantify the enhancing effect of IKLT on temporal processing with several measures: signal-to-noise ratio (SNR), reverse correlation or spike-triggered averaging of input currents, and interaural time difference (ITD) tuning curves. To characterize how IKLT, which activates below spike threshold, influences a neuron’s voltage rise toward threshold, i.e., how it filters the inputs, we focus first on the response to weak and noisy signals. Cells and models were stimulated with a computer-generated steady barrage of random inputs, mimicking weak synaptic conductance transients (the “noise”), together with a larger but still subthreshold postsynaptic conductance, EPSG (the “signal”). Reduction of IKLT decreased the SNR, mainly due to an increase in spontaneous firing (more “false positive”). The spike-triggered reverse correlation indicated that IKLT shortened the integration time for spike generation. IKLT also heightened the model’s timing selectivity for coincidence detection of simulated binaural inputs. Further, ITD tuning is shifted in favor of a slope code rather than a place code by precise and rapid inhibition onto MSO cells (Brand et al. 2002). In several ways, low-threshold outward currents are seen to shape integration of weak and strong signals in auditory neurons.

Cellular signalling properties in microcircuits

Molecules and cells are the signalling elements in microcircuits. Recent studies have uncovered bewildering diversity in postsynaptic signalling properties in all areas of the vertebrate nervous system. Major effort is now being invested in establishing the specialized signalling properties at the cellular and molecular levels in microcircuits in specific brain regions. This review is part of the TINS Microcircuits Special Feature.

Firing properties of frog tectal neurons in vitro.

Whole-cell recordings from frog tectal slices revealed different types of neuronal firing patterns in response to prolonged current injection. The patterns included regular spiking without adaptation, accelerating firing, adapting spiking, repetitive bursting and phasic response with only one spike. The observed firing patterns are similar to those found in the mammalian superior colliculus. The frog tectum could be a useful preparation in elucidating the relationship between neuronal function and membrane properties.

Spatial synchronization of visual stimulus-evoked gamma frequency oscillations in the rat superior colliculus.

In the superior colliculus, visual stimuli can induce gamma frequency oscillations of neuronal activity. It has been shown that in cats, these oscillations are synchronized over distances of greater than 300 &mgr;m that may contribute toward visual information processing. We investigated the spatial properties of such oscillations in a rodent because the availability of molecular tools could enable future studies on the role of these oscillations in visual information processing. Using extracellular electrode array recordings in anesthetized rats, we found that visual stimuli-induced gamma and eta frequency (30–115 Hz) oscillations of the local field potential that were synchronized over distances of ∼600 µm. Multiple-unit events were phase locked to the local field potential signal and showed prominent oscillations during OFF responses. The rate of lower than 5 ms cross-electrode coincidences was in line with the response-corrected predictions for each electrode. These data suggest that the synchronized superior colliculus neuronal activity is largely network driven, whereas common synaptic inputs play a minor role.

Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic Calcium Transients in the Frog Optic Tectum Layer 6 Neurons

The superior colliculus in mammals or the optic tectum in amphibians is a major visual information processing center responsible for generation of orientating responses such as saccades in monkeys or prey catching avoidance behavior in frogs. The conserved structure function of the superior colliculus the optic tectum across distant species such as frogs, birds monkeys permits to draw rather general conclusions after studying a single species. We chose the frog optic tectum because we are able to perform whole-cell voltage-clamp recordings fluorescence imaging of tectal neurons while they respond to a visual stimulus. In the optic tectum of amphibians most visual information is processed by pear-shaped neurons possessing long dendritic branches, which receive the majority of synapses originating from the retinal ganglion cells. Since the first step of the retinal input integration is performed on these dendrites, it is important to know whether this integration is enhanced by active dendritic properties. We demonstrate that rapid calcium transients coinciding with the visual stimulus evoked action potentials in the somatic recordings can be readily detected up to the fine branches of these dendrites. These transients were blocked by calcium channel blockers nifedipine CdCl2 indicating that calcium entered dendrites via voltage-activated L-type calcium channels. The high speed of calcium transient propagation, >300 μm in <10 ms, is consistent with the notion that action potentials, actively propagating along dendrites, open voltage-gated L-type calcium channels causing rapid calcium concentration transients in the dendrites. We conclude that such activation by somatic action potentials of the dendritic voltage gated calcium channels in the close vicinity to the synapses formed by axons of the retinal ganglion cells may facilitate visual information processing in the principal neurons of the frog optic tectum.

Development of a paradigm to investigate mechanisms of divided and selective attention impairment in the rodent models of Alzheimer’s disease

In Alzheimer’s disease impaired attention can be detected almost immediately after the first signs of memory loss and is considered to be a major cause of difficulties in the patients everyday life in the early stages of Alzheimer’s disease. Several types of attention are recognized such as divided, selective and sustained attention. Selective and divided attention are impaired most in the Alzheimer’s disease patients while sustained attention remains relatively intact. However, most attention tests in animal models of Alzheimer’s disease such as the five-choice serial reaction time task evaluates sustained but not other attention types. We decided to profit from a recent finding that Alzheimer’s patients have an impaired ability to detect objects approaching on a collision course in tests for selective and divided visual attention [1,2]. Collision detection is conserved across species and is performed by specialized collision-sensitive neurons in the superior colliculus of both in humans and rodents facilitating extension to humans of the results obtained in animals. However, so far little is known about collision-sensitive neurons in rats and mice and such a visual stimulus has not been used in attention tasks in rodents. To establish a paradigm for selective and divided visual attention tests in rodents, we recorded collision sensitive neurons in the rat superior colliculus by employing tetrode extracellular recordings in male, >1 month old rats. Collision sensitive neurons in the superficial layers of the superior colliculus were identified by their ability to respond to stimuli imitating collision but not to the ones veering slightly off. Collision sensitive neurons responded well to both dark (a black image on a white background) and bright (a bright image on a dark background) stimuli. Most putative collision-sensitive neurons could be assigned to eta class. Importantly, responses of collision-sensitive neurons were highly dependent on contrast, a parameter to be used to evaluate divided attention by presenting two different collision stimuli of different contrast. We will use these tests to investigate the effects of a 2-week intracerebroventricular infusion of beta-amyloid-(1-42), a rat model of Alzheimer’s disease [3], on divided and selective attention. This work was supported by a Lithuanian Research Council grant Nr. VP1-3.1-SMM-08-K-01-022.