Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal.

Heightened distractibility is a core symptom of Attention Deficit Hyperactivity Disorder (ADHD). Effective treatment is normally with chronic orally administered psychostimulants including amphetamine. Treatment prevents worsening of symptoms but the site of therapeutic processes, and their nature, is unknown. Mounting evidence suggests that the superior colliculus (SC) is a key substrate in distractibility and a therapeutic target, so we assessed whether therapeutically-relevant changes are induced in this structure by chronic oral amphetamine. We hypothesized that amphetamine would alter visual responses and morphological measures. Six-week old healthy male rats were treated with oral amphetamine (2, 5 or 10 mg/kg) or a vehicle for one month after which local field potential and multiunit recordings were made from the superficial layers of the SC in response to whole-field light flashes in withdrawal. Rapid Golgi staining was also used to assess dendritic spines, and synaptophysin staining was used to assess synaptic integrity. Chronic amphetamine increased local field potential responses at higher doses, and increased synaptophysin expression, suggesting enhanced visual input involving presynaptic remodelling. No comparable increases in multiunit activity were found suggesting amphetamine suppresses collicular output activity, counterbalancing the increased input. We also report, for the first time, five different dendritic spine types in the superficial layers and show these to be unaffected by amphetamine, indicating that suppression does not involve gross postsynaptic structural alterations. In conclusion, we suggest that amphetamine produces changes at the collicular level that potentially stabilise the structure and may prevent the worsening of symptoms in disorders like ADHD.

Repeated intermittent oral amphetamine administration results in locomotor tolerance not sensitization.

BACKGROUND: The phenomenon of locomotor sensitization to injected amphetamine is well-characterised. The increased locomotor activity found acutely is enhanced with repeated intermittent treatment. This effect arises due to hypersensitization of the dopaminergic system and is linked to drug addiction. A clinical population exposed to chronic repeated intermittent amphetamine treatment, such as is found for attention deficit hyperactivity disorder (ADHD), may be expected to be more at risk of addiction following this treatment. However, evidence suggests the opposite may be true. This suggests the route of administration may determine the direction of effects. AIMS AND METHODS: We aimed to establish how an oral amphetamine treatment regimen, similar to that used in ADHD, impacts on locomotor activity, specifically whether tolerance or sensitization would arise. Healthy hooded Lister rats were given amphetamine (2 mg/kg, 5 mg/kg and 10 mg/kg) or a vehicle solution once daily for 4 weeks with a 5 day on, 2 day off schedule. Locomotor activity was measured on the first day of treatment to establish the acute effects and on the final day of treatment to examine the chronic effects. RESULTS: As expected, acute doses of amphetamine increased locomotor activity, although this only reached statistical significance for the 5 mg/kg and 10 mg/kg doses. By contrast, after chronic treatment, animals administered these doses showed reduced activity indicating drug tolerance rather than sensitization had occurred. CONCLUSION: We suggest that the route of administration used in ADHD, which results in more stable and longer duration drug levels in the blood, results in tolerance rather than sensitization and that this effect could explain the reduced likelihood of substance addiction in those treated with psychostimulants for ADHD.

Chronic amphetamine treatment affects collicular-dependent behaviour.

Distractibility can be defined as an attention deficit where orientation toward irrelevant targets cannot be inhibited. There is now mounting evidence that the superior colliculus is a key neural correlate of distractibility, with increased collicular-activity resulting in heightened distractibility. Heightened distractibility is reduced by amphetamine, which acutely suppresses collicular responsiveness. However, when amphetamine is used to treat distractibility, it is given chronically, yet no data exist on whether chronic amphetamine treatment affects the colliculus. Here, the effect of chronic amphetamine treatment was assessed in healthy hooded lister rats on two collicular dependent behaviours following a twenty-eight day treatment period: i) orienting to visual stimuli, and ii) height-dependent modulation of air-righting. We found no significant impact of amphetamine treatment on visual orienting despite showing dose-dependent decreases in orienting to repeated stimuli. However, we did find that treatment with amphetamine significantly reduced the ability to modulate righting according to the height the animal is dropped from - a function known to be dependent on the colliculus. We suggest that the results are in line with previous research showing acute amphetamine suppresses collicular activity and we speculate that the psychostimulant may increase receptive field size, altering time-to-impact calculations carried out by the colliculus during air-righting.

Nonlinear optics in photonic nanowires.

We review recent research on nonlinear optical interactions in waveguides with sub-micron transverse dimensions, which are termed photonic nanowires. Such nanowaveguides, fabricated from glasses or semiconductors, provide the maximal confinement of light for index guiding structures enabling large enhancement of nonlinear interactions and group-velocity dispersion engineering. The combination of these two properties make photonic nanowires ideally suited for many nonlinear optical applications including the generation of single-cycle pulses and optical processing with sub-mW powers.

Ultra-low power parametric frequency conversion in a silicon microring resonator.

We demonstrate parametric wavelength conversion via four-wave mixing using ultra-low peak pump powers of a few milliwatts in a micrometer-scale silicon device. The response time of our device is 100 ps allowing for implementation in high-bandwidth optical communications. At these ultra-low power levels and microscale sizes, it should be possible to realize hundreds of these devices operating simultaneously on a single chip.

Optical time lens based on four-wave mixing on a silicon chip.

We propose a new technique to realize an optical time lens for ultrafast temporal processing that is based on four-wave mixing in a silicon nanowaveguide. The demonstrated time lens produces more than 100 pi of phase shift, which is not readily achievable using electro-optic phase modulators. Using this method we demonstrate 20x magnification of a signal consisting of two 3 ps pulses, which allows for temporal measurements using a detector with a 20 GHz bandwidth. Our technique offers the capability of ultrafast temporal characterization and processing in a chip-scale device.

All-optical regeneration on a silicon chip.

We demonstrate optical 2R regeneration in an integrated silicon device consisting of an 8-mm-long nanowaveguide followed by a ring-resonator bandpass filter. The regeneration process is based on nonlinear spectral broadening in the waveguide and subsequent spectral filtering through the ring resonator. We measure the nonlinear power transfer function for the device and find an operating peak power of 6 W. Measurements indicate that the output pulse width is determined only by the bandwidth of the bandpass filter. Numerical modeling of the nonlinear process including free-carrier effects shows that this device can be used for all-optical regeneration at telecommunication data rates.

Broad-band continuous-wave parametric wavelength conversion in silicon nanowaveguides.

We demonstrate highly broad-band frequency conversion via four-wave mixing in silicon nanowaveguides. Through appropriate engineering of the waveguide dimensions, conversion bandwidths greater than 150 nm are achieved and peak conversion efficiencies of -9.6 dB are demonstrated. Furthermore, utilizing fourth-order dispersion, wave-length conversion across four telecommunication bands from 1477 nm (S-band) to 1672 nm (U-band) is demonstrated with an efficiency of -12 dB.

Broad-band optical parametric gain on a silicon photonic chip.

Developing an optical amplifier on silicon is essential for the success of silicon-on-insulator (SOI) photonic integrated circuits. Recently, optical gain with a 1-nm bandwidth was demonstrated using the Raman effect, which led to the demonstration of a Raman oscillator, lossless optical modulation and optically tunable slow light. A key strength of optical communications is the parallelism of information transfer and processing onto multiple wavelength channels. However, the relatively narrow Raman gain bandwidth only allows for amplification or generation of a single wavelength channel. If broad gain bandwidths were to be demonstrated on silicon, then an array of wavelength channels could be generated and processed, representing a critical advance for densely integrated photonic circuits. Here we demonstrate net on/off gain over a wavelength range of 28 nm through the optical process of phase-matched four-wave mixing in suitably designed SOI channel waveguides. We also demonstrate wavelength conversion in the range 1,511-1,591 nm with peak conversion efficiencies of +5.2 dB, which represents more than 20 times improvement on previous four-wave-mixing efficiencies in SOI waveguides. These advances allow for the implementation of dense wavelength division multiplexing in an all-silicon photonic integrated circuit. Additionally, all-optical delays, all-optical switches, optical signal regenerators and optical sources for quantum information technology, all demonstrated using four-wave mixing in silica fibres, can now be transferred to the SOI platform.

Tailored anomalous group-velocity dispersion in silicon channel waveguides.

We present the first experimental demonstration of anomalous group-velocity dispersion (GVD) in silicon waveguides across the telecommunication bands. We show that the GVD in such waveguides can be tuned from -2000 to 1000 ps/(nm*km) by tailoring the cross-sectional size and shape of the waveguide.

Generation of correlated photons in nanoscale silicon waveguides.

.We experimentally study the generation of correlated pairs of photons through four-wave mixing (FWM) in embedded silicon waveguides. The waveguides, which are designed to exhibit anomalous group-velocity dispersion at wavelengths near 1555 nm, allow phase matched FWM and thus efficient pair-wise generation of non-degenerate signal and idler photons. Photon counting measurements yield a coincidence-to-accidental ratio (CAR) of around 25 for a signal (idler) photon production rate of about 0.05 per pulse. We characterize the variation in CAR as a function of pump power and pump-to-sideband wavelength detuning. These measurements represent a first step towards the development of tools for quantum information processing which are based on CMOS-compatible, silicon-on-insulator technology.