Cell biology of the neuron

Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways.Hardingham, G. E. et al. Nature Neurosci. 3, 405–414 (2002)

A fascinating dissociation of the effects of synaptic and extrasynaptic NMDA receptors. Whereas activation of synaptic receptors increased the expression of the transcription factor CREB and of BDNF, and led to a reduction in apoptosis, the activation of extrasynaptic receptors had the opposite effects. This dissociation highlights the relevance of signalling microdomains in neuronal biology, and the potential of extrasynaptic receptors as therapeutic targets in conditions such as stroke.

Neurodegenerative diseases

A polymorphic gene nested within an intron of the tau gene: implications for Alzheimer's disease.Conrad, C. et al. Proc. Natl Acad. Sci. USA 99, 7751–7756 (2002)

Neurofibrillary tangles in the brains of Alzheimer's disease (AD) patients contain an insoluble form of the TAU protein. However, it is not clear how the protein becomes insoluble. Conrad et al. have now identified a new gene, saitohin (STH), which contains a point mutation in many patients with late-onset AD. Interestingly, STH lies within an intron of the TAU gene, and the authors speculate that it might act in the same pathway as TAU.

Circadian rhythms

Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus.Cheng, M. Y. et al. Nature 417, 405–410 (2002)

Cheng et al. show that prokineticin 2 (PK2) meets the criteria to act as an output molecule that transmits the circadian rhythm from the suprachiasmatic nucleus (SCN) to physiological and behavioural systems. Transcription of PK2 in the SCN is regulated by core clock genes and entrained by light; the receptors for PK2 are found in the main target areas of SCN output; and administration of PK2 at night (when endogenous levels are low) suppresses wheel-running behaviour.

Learning and memory

Operant reward learning in Aplysia : neuronal correlates and mechanisms.Brembs, B. et al. Science 296, 1706–1709 (2002)

In an in vivo operant-learning paradigm, spontaneous biting movements in Aplysia were followed by stimulation of the En2 neuron (which normally fires during feeding and appears to act as a reinforcer). This led to an increase in spontaneous biting and in the excitability of a neuron, B51, in the buccal ganglion. In an in vitro analogue of the operant-learning system, plateau potentials in B51 were paired with puffs of dopamine (representing the reinforcing input from En2), and this led to a decrease in the burst threshold and an increase in input resistance of B51. These changes seem to represent a cellular correlate of operant learning.