Sensory systems

Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Coull, J. A. M. et al. Nature 424, 938–942 (2003)

By chronically constricting the sciatic nerve, the authors induced neuropathic pain in the rat and identified a reduction in expression of the K+–Cl− transporter KCC2 as the underlying mechanism. This trans-synaptic reduction led to disruption of Cl− homeostasis, and caused GABA (γ-aminobutyric acid)- and glycine-mediated neurotransmission to become excitatory instead of inhibitory, increasing the excitability of spinal neurons. Moreover, reducing the function of KCC2 in intact rats led to a reduction in the nociceptive threshold.

Systems neuroscience

Amphetamine or cocaine limits the ability of later experience to promote structural plasticity in the neocortex and nucleus accumbens. Kolb, B. et al. Proc. Natl Acad. Sci. USA 100, 10523–10528 (2003)

Do plastic changes induced by drugs of abuse interfere with the ability of experience to elicit similar changes? The authors repeatedly treated rats with amphetamine or cocaine, and found that the drugs limited the ability of an enriched environment to alter dendritic structure. This interference might relate to the cognitive deficits that are associated with drug abuse.

Psychiatric disorders

Abnormal neural synchrony in schizophrenia. Spencer, K. M. et al. J. Neurosci. 23, 7407–7411 (2003)

According to this electroencephalographic study, schizophrenia is associated with disturbances of neuronal synchronization in the gamma-frequency range. The authors asked patients to perform a task that required feature binding, and found that both the amplitude and the phase synchronization of gamma oscillations was impaired, raising the possibility that such an impairment might be related to the cognitive disturbances that characterize the disease.

Neurological diseases

A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia. Borsello, T. et al. Nature Med. 9, 1180–1186 (2003)

The authors used a peptide inhibitor to target c-Jun N-terminal kinase (JNK), which is activated as part of an excitotoxic cascade, in two animal models of cerebral ischaemia. Intracerebroventricular and systemic administration of the peptide as late as 6 h after the ischaemic episode significantly reduced brain damage and activation of the JNK pathway. These results indicate that JNK is a valid drug target for anti-ischaemic drugs, and highlight the potential of the peptide inhibitor as therapeutic agent.