In Brief

Neuropathology

The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling. Nicole, O. et al. Nature Med. 7, 59–64 (2001)

Although tissue-plasminogen activator (TPA) is used to treat ischaemic stroke, negative effects of this protein have also been reported. Here the authors highlight the ambivalence of TPA as a therapeutic agent by showing that TPA cleaves the NMDAR1 receptor subunit, enhances NMDA-induced Ca²⁺ influx and increases cell death. As neuron depolarization can induce TPA release, their data also indicate that endogenous TPA might potentiate the excitotoxic damage seen after episodes of ischaemia.

Snynaptic Phsiology

Fine tuning of an auditory synapse for speed and fidelity: developmental changes in presynaptic waveform, EPSC kinetics, and synaptic plasticity. Taschenberger, H. & von Gersdorff, H. J. Neurosci. 20, 9162–9173 (2000)

The calyx of Held synapse participates in sound localization. The accuracy of this synapse depends on its rapid and sustained function, but recordings from the calyx before the onset of hearing had shown synaptic depression upon repetitive activity. The authors explored whether the calyx undergoes functional changes around the onset of hearing and found several modifications that would favour synaptic speed while preventing depression: action potentials became briefer, excitatory synaptic currents were faster and the releasable pool of synaptic vesicles increased in size.

Development

The autoregulation of retinal ganglion cell number. González-Hoyuela, M. et al. Development 128, 117–124 (2001)

During eye development, retinal ganglion cells (RGCs) regulate their own number through a negative feedback signalling loop, and the molecules involved are beginning to be identified. The authors showed that nerve growth factor (NGF) is one of the molecules involved in this loop. They found that, in the developing chick, RGCs secrete NGF, which limits further RGC differentiation and kills any ganglion cells that migrate into the retina.

Cell biology of the neuron

Oligomerization of opioid receptors with β₂-adrenergic receptors: a role in trafficking and mitogen-activated protein kinase activation. Jordan, B. A. et al. Proc. Natl Acad. Sci. 98, 343–348 (2001)

The formation of G-protein-coupled heteromeric receptors results in functional changes in the interacting partners. Here the authors show that δ-opioid and β₂-adrenergic receptors can form heteromers, and that heteromer formation affects membrane trafficking of the complex. This is a novel example of the functional effects of heteromerization, and show that receptors coupled to stimulatory and inhibitory G proteins can form complexes.