Can Optogenetic Tools Determine the Importance of Temporal Codes to Sensory Information Processing in the Brain?

There is no doubt that optogenetic tools caused a paradigm shift in many fields of neuroscience. These tools enable rapid and reversible intervention with a specific neuronal circuit and then the impact on the remaining circuit and/or behavior can be studied. However, so far the ability of these optogenetic tools to interfere with neuronal signal transmission in the time scale of milliseconds has been used much less frequently although they may help to answer a fundamental question of neuroscience: how important temporal codes are to information processing in the brain. This perspective paper examines why optogenetic tools were used so little to perturb or imitate temporal codes. Although some technical limitations do exist, there is a clear need for a systems approach. More research about action potential pattern formation by interactions between several brain areas is necessary in order to exploit the full potential of optogenetic methods in probing temporal codes

Limited Spatial Spread Explains the Dependence of Visual Response Adaptation on Stimulus Size in Rat Superior Colliculus Neurons

Although adaptation to light occurs in the eye and mainly preserves the full dynamic range of neuronal responses during changing background illumination, it affects the entire visual system and helps to optimize visual information processing. We have shown recently that in rat superior colliculus (SC) neurons adaptation to light acts as a local low-pass filter because, in contrast to the primate SC, in rat collicular neurons adaptation to small stimuli is largely limited to the vicinity of the adaptor stimulus. However, it was unclear whether large visual stimuli would induce the same spatially limited adaptation. We addressed this question by evaluating the effects of 1.8°, 6.2° and 20.8° wide adaptor stimuli on test stimuli of variable size. Single unit recordings in the adult rat SC were employed to estimate the response amplitude. Small, 1.8° and 6.2° adaptors habituated visual responses only to stimuli smaller than the adaptive stimuli. However, the 20.8° adaptor dramatically reduced responses even to test stimuli >3 times wider than the adaptor (up to 70° wide). The latter result may be explained by a nearly complete occlusion by a large adaptor of the neuron's receptive field (RF). All these results are consistent with the idea of a limited spatial spread of adaptation in rat SC neurons that is the consequence of high convergence of retinal inputs, in which small RFs limit the spatial spread of adaptation. It is concluded that, in this limited spatial spread of adaptation, rodent SC resembles higher visual system areas in primates and indicates potential differences in visual information processing between rodents and primates

Result analysis of surgically treated pressure ulcers.

Pressure ulcer is a local ischaemic lesion which can affect skin, subcutaneous and deeper tissue. It occurs because of disrupted blood flow, lack of oxygen supply or malnutrition of the underlying tissue. The main cause of all these factors is unrelieved pressure on the skin. Most vulnerable are the elderly patients and those with impaired movement. Most common pressure ulcers are located in the area of sacrum, greater trochanter, heels. Quite often pressure ulcers are treated surgically. Pressure ulcers tend to reoccur and that is a huge problem. Because of that patients should thoroughly rely on the recommendations given by their health care professionals

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

Rat superior colliculus neurons respond to large visual stimuli flashed outside the classical receptive field

<div><p>Spatial integration of visual stimuli is a crucial step in visual information processing yet it is often unclear where this integration takes place in the visual system. In the superficial layers of the superior colliculus that form an early stage in visual information processing, neurons are known to have relatively small visual receptive fields, suggesting limited spatial integration. Here it is shown that at least for rats this conclusion may be wrong. Extracellular recordings in urethane-anaesthetized young adult rats (1.5–2 months old) showed that large stimuli of over 10° could evoke detectable responses well outside the borders of ‘classical’ receptive fields determined by employing 2° – 3.5° stimuli. The presence of responses to large stimuli well outside these ‘classical’ receptive fields could not be explained neither by partial overlap between the visual stimulus and the receptive field, nor by reflections or light dispersion from the stimulation site. However, very low frequency (<0.1 Hz) residual responses to small stimuli presented outside the receptive field may explain the obtained results if we assume that the frequency of action potentials during a response to a stimulus outside RF is proportional to the stimulus area. Thus, responses to large stimuli outside RF may be predicted by scaling according to the stimulus area of the responses to small stimuli. These data demonstrate that neurons in the superficial layers of the superior colliculus are capable of integrating visual stimuli over much larger area than it can be deduced from the classical receptive field.</p></div

Large flashing spots evoked neuronal activity over much wider visual field area than small spots.

<p><i>(A</i>) Trace samples of responses evoked by 2-degree spots. Trace position corresponds to the stimulus location on the monitor. Each trace is 2.0 s long; a 0.6 s stimulus was presented 0.4 s from the trace start. Grey filled circles with letters correspond to marked 15-degree stimulus locations shown in <i>B</i> and <i>C</i>. (<i>B)</i> and (<i>C</i>) Trace samples of responses evoked by 15-degree spots. Grey background bars indicate when the stimulus was presented. Letters by traces indicate responses corresponding to stimuli presented at locations shown in <i>A</i>. Scale bars are 250 μV and 2 s.</p

Action potentials actively propagating along dendrites are responsible for calcium concentration transients detected by OGB-1 dye.

<p><b><i>A</i></b>. All detected Ca_i²⁺ increases coincided with action potentials. In this trace three action potentials correspond to three steps of OGB-1 signal increases. <b><i>B</i></b>. During current injection all 7 action potentials caused OGB-1 fluorescence intensity increases. <b><i>C</i></b>. The first action potential from B is shown on faster time scale with a corresponding OGB-1 fluorescence signal. It is clear that all increase in OGB-1 fluorescence occurred within few milliseconds of the action potential occurrence. The fluorescence sampling rate was 440 Hz. The vertical bar serves as a scale for both the voltage (20 mV) relative fluorescence change, dF/F, 5%. <b><i>D E</i></b>. Calcium influx was similar during action potentials evoked by a voltage step a visual stimulus. In <b><i>D</i></b> current traces evoked by a visual stimulus (a ~20° wide black circle in the center of the receptive field) during voltage steps (a 40 mV, 20 ms long voltage step, bottom black traces) are shown in slow in fast time scales (left right panels correspondingly). Leak currents capacitance charging transients were subtracted for clarity. In <b><i>E</i></b> fluorescence traces for both conditions are aligned at the onset of the responses. Grey filled circles correspond to visually evoked stimulus while black filled circles correspond to voltage step comm. In addition, a fluorescence trace corresponding to OFF visual stimulus is shown as a dark grey line. Although no membrane currents are shown for this stimulation, two action potentials were also evoked during this OFF stimulus albeit with larger interval that explains slightly slower rate of rise of the fluorescence signal. For all three conditions the fluorescence measurements were taken in the same dendrite section at about 100 μm from the soma. <b><i>F G</i></b>. OGB-1 fluorescence increase could be detected up to >300 μm from the soma in the area of fine dendritic branches near the edge of the optic tectum. In all three locations the onset of the OGB-1 signal increase was nearly simultaneous, probably limited by the fluorescence signal sampling rate of 100 Hz. A vertical thick grey broken line in <b><i>G</i></b> denotes the onset of the inward synaptic currents while the horizontal thin black broken line denotes the 0 pA baseline for the current trace.</p

Summary of single unit properties that were tested for RF area increase with larger stimulus.

<p><i>(A</i>) A plot of all tested single unit RF area of ON responses for small, 1.5° – 3.7° in diameter stimuli (filled circles on the left) and for 15° stimuli (filled circles on the right). RF area is represented as an average RF diameter (a square root of the RF area multiplied by a factor of 4/π). Median values of diameter are shown for both stimulus sizes. Units, for which no significant increase in RF area was detected, are in grey (only an increase in RF area that could not be accounted by stimuli overlap was considered as significant). An asterisk marks a unit, for which no significant responses to large stimuli could be detected. <i>(B</i>) The same as in A but for OFF responses. (<i>C)</i> and (<i>D</i>) The ON (<i>C</i>) and the OFF (<i>D</i>) response magnitude of all tested units plotted against the size of a round stimulus presented in the center of RF. Response magnitudes are normalized to the maximum response. Grey lines indicate units with no RF area increase while black lines correspond to the units with RF area increase (for ON responses in C and OFF responses in <i>D</i>). (E) The distribution of the ON to OFF response magnitude ratio in this figure neurons.</p

Gaussian fit model reproduces in part the responses in the RF but not outside RF.

<p>(<i>A</i>) PSTH for 2° spots. (<i>B</i>) The ON response magnitude (<i>Ba</i>), its Gaussian fit (<i>Bb</i>) and the residual of the fit (<i>Bc</i>). The response magnitude for all panels is represented in grey scale shown in the lower left corner. (<i>C</i>) Responses to the spots of different sizes flashed in RF. Spot location and its size are shown as black circles (<i>Ca</i>). The real response data (filled circles) and the model predictions (broken line) are plotted as response magnitude against the spot size (<i>Cb</i>). (<i>D</i>) The same as in <i>C</i> for the outside RF stimulus.</p

The recorded calcium transients could be detected only on the dendritic branches of the patch-clamped neuron.

<p><b><i>A</i></b>. Calcium indicator OGB-1 fluorescence signals in response to several action potentials are shown for soma (black dots) a proximal dendritic branch (grey dots). In Aa absolute values of intensity are shown while in <b><i>Ab</i></b> fluorescence intensity values were normalized to the soma the dendritic branch image intensity values. <b><i>B</i></b>. A section of the proximal dendritic branch is shown as an image its fluorescence intensity profile along grey line is shown in <b><i>C</i></b>. In <b><i>D</i></b> for each pixel the image fluorescence intensity value before stimulus is plotted against a change in the fluorescence intensity during stimulation. A grey line represents a linear fit of all data points.</p