Infrared neural stimulation and inhibition using an implantable silicon photonic microdevice

Brain is one of the most temperature sensitive organs. Besides the fundamental role of temperature in cellular metabolism, thermal response of neuronal populations is also significant during the evolution of various neurodegenerative diseases. For such critical environmental factor, thorough mapping of cellular response to variations in temperature is desired in the living brain. So far, limited efforts have been made to create complex devices that are able to modulate temperature, and concurrently record multiple features of the stimulated region. In our work, the in vivo application of a multimodal photonic neural probe is demonstrated. Optical, thermal, and electrophysiological functions are monolithically integrated in a single device. The system facilitates spatial and temporal control of temperature distribution at high precision in the deep brain tissue through an embedded infrared waveguide, while it provides recording of the artefact-free electrical response of individual cells at multiple locations along the probe shaft. Spatial distribution of the optically induced temperature changes is evaluated through in vitro measurements and a validated multi-physical model. The operation of the multimodal microdevice is demonstrated in the rat neocortex and in the hippocampus to increase or suppress firing rate of stimulated neurons in a reversible manner using continuous wave infrared light (λ = 1550 nm). Our approach is envisioned to be a promising candidate as an advanced experimental toolset to reveal thermally evoked responses in the deep neural tissue

Phasic, nonsynaptic GABA-A receptor-mediated inhibition entrains thalamocortical oscillations.

GABA-A receptors (GABA-ARs) are typically expressed at synaptic or nonsynaptic sites mediating phasic and tonic inhibition, respectively. These two forms of inhibition conjointly control various network oscillations. To disentangle their roles in thalamocortical rhythms, we focally deleted synaptic, γ2 subunit-containing GABA-ARs in the thalamus using viral intervention in mice. After successful removal of γ2 subunit clusters, spontaneous and evoked GABAergic synaptic currents disappeared in thalamocortical cells when the presynaptic, reticular thalamic (nRT) neurons fired in tonic mode. However, when nRT cells fired in burst mode, slow phasic GABA-AR-mediated events persisted, indicating a dynamic, burst-specific recruitment of nonsynaptic GABA-ARs. In vivo, removal of synaptic GABA-ARs reduced the firing of individual thalamocortical cells but did not abolish slow oscillations or sleep spindles. We conclude that nonsynaptic GABA-ARs are recruited in a phasic manner specifically during burst firing of nRT cells and provide sufficient GABA-AR activation to control major thalamocortical oscillations

Synergistic activity between primary visual neurons

Abstract : Cortical microcircuitry plays a pivotal role in encoding sensory information reaching the cortex. However, the fundamental knowledge concerning the mechanisms that govern feature-encoding by these sub-networks is still sparse. Here, we show through multi electrode recordings in V1 of conventionally prepared anesthetized cats, that an avalanche of synergistic neural activity occurs between functionally connected neurons in a cell assembly in response to the presented stimulus. The results specifically show that once the reference neuron spikes in a connected neuron-pair, it facilitates the response of its companion (target) neuron for 50 ms and, thereafter, the excitability of the target neuron declines. On the other hand, the functionally unconnected neurons do not facilitate each other’s activity within the 50 ms time-window. The added excitation (facilitation) of connected neurons is almost four times the responsiveness of unconnected neurons. This suggests that connectedness confers the added excitability to neurons; consequently leading to feature-encoding within the emergent 50 ms-period. Furthermore, the facilitation significantly decreases as a function of orientation selectivity spread

Inverse Current Source Density Method in Two Dimensions: Inferring Neural Activation from Multielectrode Recordings

The recent development of large multielectrode recording arrays has made it affordable for an increasing number of laboratories to record from multiple brain regions simultaneously. The development of analytical tools for array data, however, lags behind these technological advances in hardware. In this paper, we present a method based on forward modeling for estimating current source density from electrophysiological signals recorded on a two-dimensional grid using multi-electrode rectangular arrays. This new method, which we call two-dimensional inverse Current Source Density (iCSD 2D), is based upon and extends our previous one- and three-dimensional techniques. We test several variants of our method, both on surrogate data generated from a collection of Gaussian sources, and on model data from a population of layer 5 neocortical pyramidal neurons. We also apply the method to experimental data from the rat subiculum. The main advantages of the proposed method are the explicit specification of its assumptions, the possibility to include system-specific information as it becomes available, the ability to estimate CSD at the grid boundaries, and lower reconstruction errors when compared to the traditional approach. These features make iCSD 2D a substantial improvement over the approaches used so far and a powerful new tool for the analysis of multielectrode array data. We also provide a free GUI-based MATLAB toolbox to analyze and visualize our test data as well as user datasets

A Multi-Component Model of the Developing Retinocollicular Pathway Incorporating Axonal and Synaptic Growth

During development, neurons extend axons to different brain areas and produce stereotypical patterns of connections. The mechanisms underlying this process have been intensively studied in the visual system, where retinal neurons form retinotopic maps in the thalamus and superior colliculus. The mechanisms active in map formation include molecular guidance cues, trophic factor release, spontaneous neural activity, spike-timing dependent plasticity (STDP), synapse creation and retraction, and axon growth, branching and retraction. To investigate how these mechanisms interact, a multi-component model of the developing retinocollicular pathway was produced based on phenomenological approximations of each of these mechanisms. Core assumptions of the model were that the probabilities of axonal branching and synaptic growth are highest where the combined influences of chemoaffinity and trophic factor cues are highest, and that activity-dependent release of trophic factors acts to stabilize synapses. Based on these behaviors, model axons produced morphologically realistic growth patterns and projected to retinotopically correct locations in the colliculus. Findings of the model include that STDP, gradient detection by axonal growth cones and lateral connectivity among collicular neurons were not necessary for refinement, and that the instructive cues for axonal growth appear to be mediated first by molecular guidance and then by neural activity. Although complex, the model appears to be insensitive to variations in how the component developmental mechanisms are implemented. Activity, molecular guidance and the growth and retraction of axons and synapses are common features of neural development, and the findings of this study may have relevance beyond organization in the retinocollicular pathway

Mechanism of nitric oxide-induced contraction in the rat isolated small intestine

1. The contractile response to nitric oxide (NO) in ral ileal myenteric plexus-longitudinal muscle strips was pharmacologically analysed. 2. NO (10(−7) M) induced only contraction while 10(−6) M NO induced contraction followed by relaxation. Methylene blue (up to 10(−4) M) did not affect the NO-induced contractions but significantly reduced the relaxation evoked by 10(−6) M NO. Administration of 8-bromo-cyclic GMP (10(−6)–10(−4) M) only induced relaxation. 3. Sodium nitroprusside (SNP; 10(−7)–10(−5) M) induced concentration-dependent contractions per se; the contractile response to NO, administered within 10 min after SNP, was concentration-dependently reduced. The guanosine 3′:5′-cyclic monophosphate (cyclic GMP) content of the tissues was not increased during contractions with 10(−8) M NO and 10(−6) M SNP; it was increased by a factor of 2 during contraction with 10(−7) M NO, and by a factor of 12 during relaxation with 3×10(−6) M NO. 4. The NO-induced contractions were not affected by ryanodine (3×10(−5) M) but were concentration-dependently reduced by nifedipine (10(−8)–10(−7) M) and apamin (3×10(−9)–3×10(−8) M). 5. These results suggest that cyclic GMP is not involved in the NO-induced contraction in the rat small intestine. The NO-induced contraction is related to extracellular Ca(2+) influx through L-type Ca(2+) channels, that might be activated in response to the closure of Ca(2+)-dependent K(+) channels

Involvement of endogenous tachykinins and CGRP in the motor responses produced by capsaicin in the guinea-pig common bile duct.

In functional experiments, we have investigated the effect exerted by neurotransmitters released from capsaicin-sensitive primary afferent nerve terminals in the isolated guinea-pig common bile duct. In resting preparations, capsaicin (0.1 μM) produced a quick contraction (45.1±4% of KCl 80 mM) which was abolished by either atropine (1 μM) or tetrodotoxin (0.5 μM). The tachykinin receptor-selective antagonists GR 82334 (NK1 receptor-selective; 3 μM), MEN 11420 (NK2 receptor-selective; 1 μM) and sR 142801 (NK3 receptor-selective; 0.1 μM) administered separately failed to reduce the capsaicin-evoked contraction, whereas any combination of the three antagonists was effective: GR 82334 plus MEN 11420, 36±7% reduction; GR 82334 plus SR 142801, 48±4% reduction; MEN 11420 plus SR 142801, 55±3% reduction; GR 82334 plus MEN 11420 plus SR 142801, 57±5% reduction. Neither the CGRP1 receptor antagonist h-CGRP (8-37) (1.5 μM) nor the P(2x) purinoceptor antagonist PPADS (50 μM) affected the contractile response to capsaicin. The effect of capsaicin (0.1 μM) was abolished by pretreatment with capsaicin itself (10 μM for 15 min). Human calcitonin gene-related peptide (h-CGRP; 0.1 μM) mimicked the effect of capsaicin on resting preparations (contractile response =28% of KCl 80 mM). In preparations precontracted with a submaximal concentration of KCl (24 mM), and in the presence of atropine (1 μM), GR 82334 (3 μM) and MEN 11420 (3 μM), capsaicin (1 μM) produced a tetrodotoxin-insensitive long-lasting relaxation (45±3% reduction of tone, at 4 min from administration), which was unaffected by the nitric oxide (NO) synthase inhibitor, L-NOARG (100μM). h- CGRP (10-50 nM) produced a similar sustained relaxation of precontracted preparations (59±4% reduction of tone). h-CGRP (8-37) (1.5 μM) almost completely reversed file relaxations produced by both capsaicin and h-CGRP. Application of electrical field stimulation (EFS: trains of stimuli of 10 Hz; 0.25 ms pulse width; supramaximal voltage; for 60 s) to precontracted preparations produced a sustained, tetrodotoxin (1 μM)-sensitive relaxation (32±4% reduction of tone). L-NOARG (100 μM) greatly reduced (69±5% inhibition) the EFS-elicited relaxation. A complete reversal of the relaxant response to EFS into a contraction was obtained by administering L-NOARG to preparations in which a functional blockade of capsaicin-sensitive primary afferent neurons had been achieved by incubating the tissue with capsaicin (10 μM) for 15 min. At immunohistochemistry, tachykinin- and CGRP- immunoreactivities (TK-IR/CGRP-IR) were detected in varicose nerve fibers throughout the common bile duct, while TK-IR cell bodies were observed in the terminal portion (ampulla) only. In vivo pretreatment with capsaicin (50 mg/kg; 6-7 days before) decreased the number of CGRP-IR nerves, whereas the TK-IR neural network was apparently unchanged. In conclusion, our data provide functional evidence for the presence of capsaicin-sensitive primary afferent nerve endings in the guinea-pig terminal biliary tract, whose stimulation by capsaicin or EFS produces the release of tachykinins and CGRP. In addition, morphological evidence is provided that the bulk of TK-IR material in the biliary tract is contained in intrinsic neuronal elements, while CGRP in this tissue is of extrinsic origin only. Tachykinins, probably released in small amounts by capsaicin, act by activating receptors of the NK1, NK2 and NK3 type, most probably located on intrinsic cholinergic neurons, which in turn release ACh to produce the final excitatory motor response. The contractile response to capsaicin obtained in the presence of the three tachykinin receptor antagonists could be due to the co-released CGRP and/or to other unknown neurotransmitters. CGRP produces either indirect excitatory or direct inhibitory responses by stimulation of CGRP2 and CGRP1 receptors, respectively