Addiction assignment

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Electric field

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Metal bar

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process. In the rest frame of the electron, the charged impurity rushing towards it consti- tutes a current filament, so the electron ‘sees’ a weak magnetic field circling the filament. This non-uniform magnetic field imparts a force on the electron along a direction that depends on its spin orientation3,4. The net result is that spin-up electrons are pushed to the right of the impurity whereas spin-down electrons are pushed to its left.

In effect, each impurity acts like a spin filter that selectively kicks electrons to one side or the other, depending on their spin. As shown in Figure 1c, the excess spin-up population in the incident beam results in more charge accumulating on the far face than on the near face of the platinum film. The voltage differ- ence between the two faces is observable as a Hall signal. The asymmetric scattering of electrons is especially large in materials with a high atomic number, such as platinum. Fol- lowing its prediction3,4, the spin Hall effect was first observed by applying purely optical tech- niques to semiconductors5,6, and was later detected electrically in metals7,8.

In a series of tests, Uchida et al.2 convincingly show that the Hall voltage in the platinum film arises from the spin voltage. The Hall signal in

the platinum film tracks both the magnitude and the direction of the magnetization in the nickel–iron film. Moreover, by moving the platinum film along the length of the nickel– iron film, they show that the spin voltage varies linearly over the 6-mm length of the sample. In demonstrating that the spin Seebeck effect can produce a large, calibrated spin-voltage source that can be ‘tapped’ anywhere along the length of the ferromagnet, Uchida and colleagues have added an important tool to the spintronics toolbox. ■ N. P. Ong is in the Department of Physics, Princeton University, Princeton, New Jersey 08544, USA. e-mail: [email protected]

1. Gregg, J. F. in Spin Electronics (eds Ziese, M. & Thornton, M. J.) 3–31 (Springer, 2001).

2. Uchida, K. et al. Nature 455, 778–781 (2008). 3. D’yakonov, M. I. & Perel, V. I. Phys. Lett. A 35, 459–460

(1971). 4. Hirsch, J. E. Phys. Rev. Lett. 83, 1834–1837 (1999). 5. Kato, Y. K., Myers, R. C., Gossard, A. C. & Awschalom, D. D.

Science 306, 1910–1913 (2004). 6. Wunderlich, J., Kaestner, B., Sinova, J. & Jungwirth, T.

Phys. Rev. Lett. 94, 047204 (2005). 7. Valenzuela, S. O. & Tinkham, M. Nature 442, 176–179

(2006). 8. Kimura, T., Otani, Y., Sato, T., Takahashi, S. & Maekawa, S.

Phys. Rev. Lett. 98, 156601 (2007).

Figure 1 | The spin Seebeck effect. a, In the ordinary Seebeck effect, a temperature gradient in a metal bar causes more electrons to accumulate at the cool end, producing a tilt in the chemical potential (μ), which is observable as an electric field. b, Uchida et al.2 extend the Seebeck effect to spins. In a ferromagnet, the temperature gradient results in an excess of spin-up electrons at the cool end, and an excess of spin-down electrons at the warm end. Their respective spin- chemical potentials, μ and μ , have tilt profiles of opposite signs (solid lines), the average (dashed line) giving the electric field. c, The spin Hall effect. The excess of spin-up electrons (red arrows) at the cool end of the ferromagnet drives a spin current that flows vertically into the platinum film (yellow arrow). Here, spin-up means that the direction of the spin is parallel to the magnetic field, and thus points to the right. By spin–orbit coupling, electrons ‘see’ a weak magnetic field circulating around a charged impurity (circles around blue dot). Scattering from the charged impurity causes spin-up electrons to accumulate preferentially on the far face of the platinum film, whereas spin-down electrons (blue arrows) end up on the near face. The imbalance is observed as a Hall voltage difference between the two faces.

NEUROSCIENCE

Brain’s defence against cocaine L. Judson Chandler and Peter W. Kalivas

Long-term exposure to cocaine changes the organization of synaptic connections within the addiction circuitry of the brain. This process might protect against the development and persistence of addiction.

Neurons modify their structure and communi- cation with other neurons in response to experiences. Such experience-dependent neuro plasticity is crucial for survival because it allows learning from, and responses to, changes in the environment. But the cellular mechanisms that mediate this process can also be co-opted by drugs of abuse. Reporting in Neuron, Pulipparacharuvil et al.1 describe how some of the chemical, structural and behav- ioural changes in neurons that are induced by repeated exposure to cocaine are regulated at a molecular level.

Drug addiction is characterized by com- pulsive drug seeking. It resembles a chronic relapsing disorder in which the addict resumes taking drugs after a period or periods of absti- nence. Human and animal studies indicate that the recalcitrant nature of addiction results from drug-induced stimulation of reward-related learning processes in the brain. The pleasure- producing effects of the drug trigger cellular and molecular processes that are normally activated by natural rewards such as food and sex. Repeated exposure to an addictive drug

leads to a long-lasting associative memory of its rewarding properties through experience- dependent neuroplasticity. In effect, drug- seeking behaviour becomes hard-wired in the addict’s brain, and the persistent memory trace is easily reactivated by drug-associated environmental stimuli, such as the sight of drug paraphernalia.

Along the dendritic processes of a neuron, morphologically specialized structures called dendritic spines receive most of the excitatory signals from other neurons through synap- tic junctions. These spines are considered to be a primary cellular site for mediating the synaptic plasticity that is thought to under- pin memory formation2. One regulator of the density of excitatory signals on dendritic spines is the gene transcription factor MEF2 (ref. 3). When active (dephosphorylated), MEF2 favours elimination of dendritic spines, and when inactive (phosphorylated) it allows spine formation3,4.

Repeated exposure to cocaine and other psychostimulants increases the number of dendritic spines on medium spiny neurons

drives a spin current into the platinum film. The decay of this spin current leads to the appearance of an electrical signal through the spin Hall effect3,4, which enables spin currents to be detected using a sensitive voltmeter.

To understand the spin Hall effect, one can track an electron as it enters the platinum film and scatters off a charged impurity (Fig. 1c). The spin–orbit interaction — the interaction between an electron’s spin and its motion — imparts a left–right asymmetry to the scattering

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in the nucleus accumbens — a primary brain region in the addiction neurocircuitry. So Pulip- paracharuvil and colleagues1 hypothesized that such cocaine-induced structural neuro plasticity might also be regulated by MEF2. Indeed, they demonstrate that this transcription factor, which is highly expressed in medium spiny neurons and is predominantly active under normal conditions1, is affected by chronic cocaine administration. Specifically, long-term exposure to cocaine seems to prevent MEF2 dephosphorylation by a calcium/calmodu- lin-dependent phosphatase enzyme known as calcineurin, thereby suppressing its activation.

Cocaine-induced MEF2 inhibition also seems to involve enhanced phosphorylation of this transcription factor by a kinase known as Cdk5. In the nucleus accumbens, Cdk5 activity — which modulates behavioural responses to cocaine, such as motivation to consume the drug5 — increases after chronic exposure to cocaine6. Together with Pulippa- racharuvil and colleagues’ data, these observa- tions4–6 strongly suggest that repeated exposure to cocaine inhibits MEF2 activity through both enhanced phosphorylation by Cdk5 and attenuation of dephosphorylation by calci- neurin. The reduction in MEF2’s transcriptional activity in turn promotes increases in the number of dendritic spines.

The basic mechanism underlying experi- ence-dependent synaptic plasticity is often described by the phrase “Neurons that fire together, wire together”7. Reward-related associative learning is a form of such ‘Hebbian plasticity’, in which synaptic connections are enhanced by the improved strength of existing

synapses and/or by an increase in the number of such connections. So a logical conclusion would be that cocaine-induced increases in spine density reflect an activity-dependent strengthening of synaptic connectivity, which presumably underlies addictive behaviour. Surprisingly, however, Pulipparacharuvil and colleagues’ observations1 do not support this inference. By manipulating MEF2 activity, they inhibited cocaine-induced increases in spine density. However, this did not seem to prevent increases in the behavioural response to this drug, and might even promote it. So increases in spine density resulting from MEF2 inhibition seem to be associated with reduced behavioural sensitivity to cocaine.

If bulk increase in spine density within the nucleus accumbens does not contribute to enhanced behavioural responses to cocaine, then what is its function, and how can it be reconciled with the processes of experience- dependent associative learning? One con- founding aspect of Hebbian plasticity is that, when allowed to proceed unchecked, activity- dependent changes in synaptic connections can destabilize neural networks8. In self- defence, the brain uses homeostatic-plasticity mechanisms to oppose such destabilizing effects.

Homeostatic plasticity tends to occur on a large scale to maintain the overall firing activ- ity of a neuron. This allows synapse-specific remodelling of neuronal circuits to proceed through Hebbian mechanisms while maintain- ing stability of the overall neural network. A major excitatory input reaching medium spiny neurons originates from the prefrontal cortex,

but chronic exposure to cocaine markedly alters the output of prefrontal cortical neurons projecting to the nucleus accumbens9. So, as Pulipparacharuvil et al. suggest, an intriguing possibility is that cocaine-induced increases in spine density in the nucleus accumbens, which are mediated by MEF2 inhibition, may represent a homeostatic response to altered excitatory input from the prefrontal cortex.

These findings1 provide a direct challenge to the view that increased spine density induced by repeated exposure to psychostimulants underlies maladaptive plasticity. More over, they agree with previous observations10 that identified compensatory drug-induced neuro- adaptations. Future research into the neuroplas- ticity induced by addictive drugs must therefore consider competition between activity-depend- ent remodelling of synaptic connections and homeostatic adaptations that maintain overall stability in neuronal networks. ■ L. Judson Chandler and Peter W. Kalivas are in the Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA. e-mails: [email protected]; [email protected]

1. Pulipparacharuvil, S. et al. Neuron 59, 621–633 (2008). 2. Alvarez, V. A. & Sabatini, B. L. Annu. Rev. Neurosci. 30,

79–97 (2007). 3. Flavell, S. W. et al. Science 311, 1008–1012 (2006). 4. Gong, X. et al. Neuron 38, 33–46 (2003). 5. Benavides, D. R. et al. J. Neurosci. 27, 12967–12976 (2007). 6. Bibb, J. A. et al. Nature 410, 376–380 (2001). 7. Bi, G. & Poo, M. Annu. Rev. Neurosci. 24, 139–166 (2001). 8. Abbott, L. F. & Nelson, S. B. Nature Neurosci. 3, 1178–1183

(2000). 9. Kalivas, P. W., Volkow, N. & Seamans, J. Neuron 45,

647–650 (2005). 10. Toda, S. et al. J. Neurosci. 26, 1579–1587 (2006).

With high oil prices sparking a surge of interest in alternative energy sources, solar cells have become the subject of intense research. Much of this effort focuses on finding new designs that open up fresh applications. John Rogers and colleagues now report just such a development (J. Yoon et al. Nature Mater. doi:10.1038/nmat2287; 2008) — tiny, ultrathin cells made of silicon that, when fixed in arrays on a flexible substrate, create large, bendy solar cells (pictured).

The authors carve their microcell arrays from a rectangular block of silicon. They begin by etching the outlines of the microcells (the tops and sides) onto the upper surface of the silicon block. They then make electronic junctions and electrical contacts by ‘doping’ the silicon,

adding boron and phosphorus, and using an inert mask to define the regions to be doped. A further round of etching exposes the final three- dimensional shape of the microcells, retaining a thin sliver of silicon to anchor the cells to the block. Finally, the base of the wafer is doped with boron, to yield functioning solar microcells.

To make bendable, large-scale solar cells, Rogers and colleagues use a printing technique. They press a flat stamp onto the arrays of microcells on the silicon block, breaking the anchors that tether them to the silicon. The microcells stick to the soft surface of the stamp, and are transferred to a flexible substrate simply by pressing the stamp onto the substrate. The authors then construct electrodes to

connect the microcells to each other, using one of various established methods.

The resulting devices have several desirable properties. First, they are remarkably light, which, along with their flexibility, allows them to be transported and installed more easily than existing solar cells. Second, they work just as efficiently when bent as they do when flat, so they could be fixed to curved or irregular surfaces. Furthermore, they can be made to be transparent, which would allow them to be used on windows. And because the microcells are so thin, less silicon is used, minimizing costs. Andrew Mitchinson

MATERIALS SCIENCE

Solar cells go round the bend

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