20 results found
Caze RD, Jarvis S, Foust AJ, et al., 2017, Dendrites Enable a Robust Mechanism for Neuronal Stimulus Selectivity, NEURAL COMPUTATION, Vol: 29, Pages: 2511-2527, ISSN: 0899-7667
Guillon M, Forget BC, Foust AJ, et al., 2017, Vortex-free phase profiles for uniform patterning with computer-generated holography, Optics Express, Vol: 25, Pages: 12640-12652
© 2017 Optical Society of America. Computer-generated holography enables efficient light pattern generation through phase-only wavefront modulation. While perfect patterning usually requires control over both phase and amplitude, iterative Fourier transform algorithms (IFTA) can achieve phase-only approximations which maximize light efficiency at the cost of uniformity. The phase being unconstrained in the output plane, it can vary abruptly in some regions leading to destructive interferences. Among such structures phase vortices are the most common. Here we demonstrate theoretically, numerically and experimentally, a novel approach for eliminating phase vortices by spatially filtering the phase input to the IFTA, combining it with phase-based complex amplitude control at the spatial light modulator (SLM) plane to generate smooth shapes. The experimental implementation is achieved performing complex amplitude modulation with a phase-only SLM. This proposed experimental scheme offers a continuous and centered field of excitation. Lastly, we characterize achievable trade-offs between pattern uniformity, diffraction efficiency, and axial confinement.
Ronzitti E, Conti R, Zampini V, et al., 2017, Submillisecond Optogenetic Control of Neuronal Firing with Two-Photon Holographic Photoactivation of Chronos., J Neurosci, Vol: 37, Pages: 10679-10689
Optogenetic neuronal network manipulation promises to unravel a long-standing mystery in neuroscience: how does microcircuit activity relate causally to behavioral and pathological states? The challenge to evoke spikes with high spatial and temporal complexity necessitates further joint development of light-delivery approaches and custom opsins. Two-photon (2P) light-targeting strategies demonstrated in-depth generation of action potentials in photosensitive neurons bothin vitroandin vivo, but thus far lack the temporal precision necessary to induce precisely timed spiking events. Here, we show that efficient current integration enabled by 2P holographic amplified laser illumination of Chronos, a highly light-sensitive and fast opsin, can evoke spikes with submillisecond precision and repeated firing up to 100 Hz in brain slices from Swiss male mice. These results pave the way for optogenetic manipulation with the spatial and temporal sophistication necessary to mimic natural microcircuit activity.SIGNIFICANCE STATEMENTTo reveal causal links between neuronal activity and behavior, it is necessary to develop experimental strategies to induce spatially and temporally sophisticated perturbation of network microcircuits. Two-photon computer generated holography (2P-CGH) recently demonstrated 3D optogenetic control of selected pools of neurons with single-cell accuracy in depth in the brain. Here, we show that exciting the fast opsin Chronos with amplified laser 2P-CGH enables cellular-resolution targeting with unprecedented temporal control, driving spiking up to 100 Hz with submillisecond onset precision using low laser power densities. This system achieves a unique combination of spatial flexibility and temporal precision needed to pattern optogenetically inputs that mimic natural neuronal network activity patterns.
Schultz SR, Copeland CS, Foust AJ, et al., 2017, Advances in Two-Photon Scanning and Scanless Microscopy Technologies for Functional Neural Circuit Imaging, PROCEEDINGS OF THE IEEE, Vol: 105, Pages: 139-157, ISSN: 0018-9219
Casale AE, Foust AJ, Bal T, et al., 2015, Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties, JOURNAL OF NEUROSCIENCE, Vol: 35, Pages: 15555-15567, ISSN: 0270-6474
Foust AJ, Zampini V, Tanese D, et al., 2015, Computer-generated holography enhances voltage dye fluorescence discrimination in adjacent neuronal structures, Neurophotonics, Vol: 2, ISSN: 2329-423X
© The Authors. Voltage-sensitive fluorescence indicators enable tracking neuronal electrical signals simultaneously in multiple neurons or neuronal subcompartments difficult to access with patch electrodes. However, efficient widefield epifluorescence detection of rapid voltage fluorescence transients necessitates that imaged cells and structures lie sufficiently far from other labeled structures to avoid contamination from out of focal plane and scattered light. We overcame this limitation by exciting dye fluorescence with one-photon computer-generated holography shapes contoured to axons or dendrites of interest, enabling widefield detection of voltage fluorescence with high spatial specificity. By shaping light onto neighboring axons and dendrites, we observed that dendritic back-propagating action potentials were broader and slowly rising compared with axonal action potentials, differences not measured in the same structures illuminated with a large "pseudowidefield" (pWF) spot of the same excitation density. Shaped illumination trials showed reduced baseline fluorescence, higher baseline noise, and fractional fluorescence transient amplitudes two times greater than trials acquired with pWF illumination of the same regions.
Foust AJ, Casale AE, Zecevic D, et al., 2012, High signal-to-noise ratio voltage imaging: A powerful tool for determining electrophysiological properties of CNS axons
Although axons play a key role in neuronal computation, the small size of CNS axons precludes direct characterization with electrical recordings. We implement high signal-to-noise atio VSD imaging to determine cortical axon functional properties. © OSA 2012.
Foust AJ, Yu Y, Popovic M, et al., 2011, Somatic membrane potential and Kv1 channels control spike repolarization in cortical axon collaterals and presynaptic boutons., J Neurosci, Vol: 31, Pages: 15490-15498
The shape of action potentials invading presynaptic terminals, which can vary significantly from spike waveforms recorded at the soma, may critically influence the probability of synaptic neurotransmitter release. Revealing the conductances that determine spike shape in presynaptic boutons is important for understanding how changes in the electrochemical context in which a spike is generated, such as subthreshold depolarization spreading from the soma, can modulate synaptic strength. Utilizing recent improvements in the signal-to-noise ratio of voltage-sensitive dye imaging in mouse brain slices, we demonstrate that intracortical axon collaterals and en passant presynaptic terminals of layer 5 pyramidal cells exhibit a high density of Kv1 subunit-containing ion channels, which generate a slowly inactivating K(+) current critically important for spike repolarization in these compartments. Blockade of the current by low doses of 4-aminopyridine or α-dendrotoxin dramatically slows the falling phase of action potentials in axon collaterals and presynaptic boutons. Furthermore, subthreshold depolarization of the soma broadened action potentials in collaterals bearing presynaptic boutons, an effect abolished by blocking Kv1 channels with α-dendrotoxin. These results indicate that action potential-induced synaptic transmission may operate through a mix of analog-digital transmission owing to the properties of Kv1 channels in axon collaterals and presynaptic boutons.
Popovic MA, Foust AJ, McCormick DA, et al., 2011, The spatio-temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study., J Physiol, Vol: 589, Pages: 4167-4187
The spatial pattern of Na(+) channel clustering in the axon initial segment (AIS) plays a critical role in tuning neuronal computations, and changes in Na(+) channel distribution have been shown to mediate novel forms of neuronal plasticity in the axon. However, immunocytochemical data on channel distribution may not directly predict spatio-temporal characteristics of action potential initiation, and prior electrophysiological measures are either indirect (extracellular) or lack sufficient spatial resolution (intracellular) to directly characterize the spike trigger zone (TZ). We took advantage of a critical methodological improvement in the high sensitivity membrane potential imaging (V(m) imaging) technique to directly determine the location and length of the spike TZ as defined in functional terms. The results show that in mature axons of mouse cortical layer 5 pyramidal cells, action potentials initiate in a region ∼20 μm in length centred between 20 and 40 μm from the soma. From this region, the AP depolarizing wave invades initial nodes of Ranvier within a fraction of a millisecond and propagates in a saltatory fashion into axonal collaterals without failure at all physiologically relevant frequencies. We further demonstrate that, in contrast to the saltatory conduction in mature axons, AP propagation is non-saltatory (monotonic) in immature axons prior to myelination.
Foust A, Popovic M, Zecevic D, et al., 2010, Action potentials initiate in the axon initial segment and propagate through axon collaterals reliably in cerebellar Purkinje neurons., J Neurosci, Vol: 30, Pages: 6891-6902
Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By using a recent improvement in voltage-sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission.
Schei JL, Foust AJ, Rojas MJ, et al., 2009, State-dependent auditory evoked hemodynamic responses recorded optically with indwelling photodiodes., Appl Opt, Vol: 48, Pages: D121-D129
Implantable optical technologies provide measurements of cerebral hemodynamic activity from freely behaving animals without movement constraint or anesthesia. In order to study state-dependent neural evoked responses and the consequential hemodynamic response, we simultaneously measured EEG and scattered light changes in chronically implanted rats. Recordings took place under freely behaving conditions, allowing us to compare the evoked responses across wake, sleep, and anesthetized states. The largest evoked electrical and optical responses occurred during quiet sleep compared to wake and REM sleep, while isoflurane anesthesia showed a large, late burst of electrical activity synchronized to the stimulus but an earlier optical response.
Foust AJ, Schei JL, Rojas MJ, et al., 2008, In vitro and in vivo noise analysis for optical neural recording., J Biomed Opt, Vol: 13, ISSN: 1083-3668
Laser diodes (LD) are commonly used for optical neural recordings in chronically recorded animals and humans, primarily due to their brightness and small size. However, noise introduced by LDs may counteract the benefits of brightness when compared to low-noise light-emitting diodes (LEDs). To understand noise sources in optical recordings, we systematically compared instrument and physiological noise profiles in two recording paradigms. A better understanding of noise sources can help improve optical recordings and make them more practical with fewer averages. We stimulated lobster nerves and a rat cortex, then compared the root mean square (RMS) noise and signal-to-noise ratios (SNRs) of data obtained with LED, superluminescent diode (SLD), and LD illumination for different numbers of averages. The LED data exhibited significantly higher SNRs in fewer averages than LD data in all recordings. In the absence of tissue, LED noise increased linearly with intensity, while LD noise increased sharply in the transition to lasing and settled to noise levels significantly higher than the LED's, suggesting that speckle noise contributed to the LD's higher noise and lower SNRs. Our data recommend low coherence and portable light sources for in vivo chronic neural recording applications.
Schei JL, Foust AJ, Rojas MJ, et al., 2008, Evoked optical response under wake, sleep, and anesthetized states
Concurrent electrical and optical measurements of auditory cortex responses exhibits state dependent hemodynamic activity. When compared to wake, quiet sleep elicits large, late optical signals, REM signals are large, while Isoflurane signals are phase shifted. © 2008 Optical Society of America.
Schei JL, McCluskey MD, Foust AJ, et al., 2008, Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light., Neuroimage, Vol: 40, Pages: 1034-1043, ISSN: 1053-8119
To identify the neural constituents responsible for generating polarized light changes, we created spatially resolved movies of propagating action potentials from stimulated lobster leg nerves using both reflection and transmission imaging modalities. Changes in light polarization are associated with membrane depolarization and provide sub-millisecond temporal resolution. Typically, signals are detected using light transmitted through tissue; however, because we eventually would like to apply polarization techniques in-vivo, reflected light is required. In transmission mode, the optical signal was largest throughout the center of the nerve, suggesting that most of the optical signal arose from the inner nerve bundle. In reflection mode, polarization changes were largest near the edges, suggesting that most of the optical signal arose from the outer sheath. In support of these observations, an optical model of the tissue showed that the outer sheath is more reflective while the inner nerve bundle is more transmissive. In order to apply these techniques in-vivo, we must consider that brain tissue does not have a regular orientation of processes as in the lobster nerve. We tested the effect of randomizing cell orientation by tying the nerve in an overhand knot prior to imaging, producing polarization changes that can be imaged even without regular cell orientations.
Foust AJ, Rector DM, 2007, Optically teasing apart neural swelling and depolarization., Neuroscience, Vol: 145, Pages: 887-899, ISSN: 0306-4522
We measured birefringence, 90 degree scattered light, and voltage sensitive dye changes from lobster walking leg nerves. Systematic application of key chemical agents revealed separate cellular mechanisms underlying fast optical signals. Each agent exhibited mixed effects, some having a greater effect on cellular swelling and refractive index, and some altering membrane potential. Birefringence changes were tightly correlated with voltage sensitive dye signals and were perturbed by those agents that altered membrane potential. Signals from light scattered at 90 degrees corroborated the hypothesis that large angle scattering signals arise from changes in the interstitial spaces and were perturbed by those agents that altered cellular swelling and refractive index. We conclude that multiple cellular mechanisms can be exploited to measure rapid optical signals. Since birefringence produces much larger changes than scattering, the use of polarized light might lead to improvements in imaging neural activity with high temporal resolution, especially since birefringence changes corresponded closely to membrane potential.
McCluskey MD, Sable JJ, Foust AJ, et al., 2007, Recording invertebrate nerve activation with modulated light changes., Pages: 1866-1871, ISSN: 1559-128X
Optical scattering techniques have the potential to provide noninvasive measurements of neural activity with good spatial and temporal resolution. We used the lobster nerve as a model system to investigate and record event-related optical signals with a modulated light source and heterodyne detection system. We observed changes in the transmitted birefringent light intensity, corresponding with electrophysiological measurements of the action potential. The photon delay was below the detection threshold, in part due to the small size of the nerve bundle. Our system allowed us to place an upper bound on the magnitude of the phase change of 0.01 degrees. The physiological stability of the preparation allows comprehensive characterization of biological and instrumentation noise sources for testing optical measurement systems.
Foust AJ, Rector DM, 2006, Optically teasing apart neural swelling and depolarization
We measured voltage sensitive dye, scattered light and birefringence from nerves during potassium channel blockade. Birefringence followed membrane voltage while scattering was slower and long lasting, dissociating cellular swelling processes from membrane potential. © 2006 Optical Society of America.
McCluskey MD, Sable JJ, Foust AJ, et al., 2006, Action potentials in invertebrate nerves studied by modulated light changes
Event-related optical signals (EROS) were obtained from electrically stimulated lobster nerves, using a modulated light source and heterodyne detection system. Changes in birefringent light intensity corresponded with electrophysiological measurements of the action potential. © 2005 Optical Society of America.
Foust AJ, Beiu RM, Rector DM, 2005, Optimized birefringence changes during isolated nerve activation., Appl Opt, Vol: 44, Pages: 2008-2012, ISSN: 1559-128X
Single trial, birefringence signals associated with action potentials from isolated lobster nerves were optimized with high-intensity light-emitting diodes (LEDs) and glass polarizers. The narrow spectral output of the LEDs allowed us to select specific wavelengths, increasing the effectiveness of the polarizers and minimizing the stray light in the system. The LEDs produced intensity profiles equivalent to narrowband filtered 100-W halogen light, and birefringence signals were comparable or superior in size and clarity to halogen lamp recordings. The results support a direct correlation between signal size and polarizer extinction coefficient. Increasing the sensitivity of birefringence detection through the use of LED light sources could ameliorate noninvasive brain imaging techniques that employ fast optical consequences associated with action potential propagation.
Yao X-C, Foust A, Rector DM, et al., 2005, Cross-polarized reflected light measurement of fast optical responses associated with neural activation., Biophys J, Vol: 88, Pages: 4170-4177, ISSN: 0006-3495
We developed an optical probe for cross-polarized reflected light measurements and investigated optical signals associated with electrophysiological activation in isolated lobster nerves. The cross-polarized baseline light intensity (structural signal) and the amplitude of the transient response to stimulation (functional signal) measured in reflected mode were dependent on the orientation of the nerve axis relative to the polarization plane of incident light. The maximum structural signal and functional response amplitude were observed at 45 degrees , and the ratio of functional to structural signals was approximately constant across orientations. Functional responses were measured in single trials in both transmitted and reflected geometries and responses had similar waveforms. Both structural and functional signals were an order of magnitude smaller in reflected than in transmitted light measurements, but functional responses had similar signal/noise ratios. We propose a theoretical model based on geometrical optics that is consistent with experimental results. In the model, the cross-polarized structural signal results from light reflection from axonal fibers and the transient functional response arises from axonal swelling associated with neural activation. Polarization-sensitive reflected light measurements could greatly enhance in vivo imaging of neural activation since cross-polarized responses are much larger than scattering signals now employed for dynamic functional neuroimaging.
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