In Brief

Neurotransmitters

Deletion of the GABA_A receptor α1 subunit increases tonic GABA_A receptor current: a role for GABA uptake transporters. Ortinski, P. I. et al. J. Neurosci. 26, 9323–9331 (2006)

Mice lacking the gene for the α1 GABA (γ-aminobutyric acid) receptor subunit type A (GABA_A), a crucial component of GABA_A-mediated synaptic neurotransmission, exhibit remarkable functional compensation: despite missing more than half the normal number of GABA_A receptors they show no overt phenotype. Ortinski et al. now show the mechanism of compensation to be an increase in 'tonic' GABA_A receptor-mediated current through high-affinity non-α1-containing receptors. The abundance of these receptors was unchanged, but the level of extrasynaptic GABA was increased owing to a decrease in GABA transporter activity.

Neurogenesis

Neocortical neurogenesis in humans is restricted to development. Bhardwaj, R. D. et al. Proc. Natl Acad. Sci. USA 103, 12564–12568 (2006)

Debate over the existence of adult-born neurons in the neocortex is compounded by difficulties in assessing neurogenesis in humans. Now, evidence has emerged showing that, in the human cortex, no new neurons are added after birth. The authors employed a technique that takes advantage of changing levels of atmospheric ¹⁴C during the twentieth century. From 1955 to 1963, ¹⁴C levels increased owing to nuclear bomb testing, then rapidly declined. These changes are reflected in the ¹⁴C content of DNA in cells becoming postmitotic during these periods. In post-mortem brain tissue, all neocortical neurons examined were demonstrated to have been present at birth, although the authors note that neurogenesis contributing to less than 1% of the total neocortical population would not have been detected by this method. These findings, together with evidence from BrdU studies, provide further evidence to suggest that neurons are not normally generated in the adult neocortex.

Neurodegenerative diseases

Ubiquitin hydrolase Uch-L1 rescues β-amyloid-induced decreases in synaptic function and contextual memory. Gong, B. et al. Cell 126, 775–788 (2006)

The ubiquitin–proteasome pathway is known to have a role in the pathogensis of Alzheimer's disease (AD). It now seems that inhibiting the activity of a component of this pathway, ubiquitin C-terminal hydrolase L1 (Uch-L1), is associated with impairments in long-term potentiation in slice cultures treated with oligomeric Aβ. Increasing Uch-L1 activity through treatment with exogenous Uch-L1 reversed this effect in the hippocampal slice cultures and in slices from App/PS1 mice. Moreover, in App/PS1 mice, exogenous delivery of Uch-L1 led to an improvement in contextual memory. Further work showed that the effect of Uch-L1 on synaptic function depended on the protein kinase A (PKA)-cyclic AMP response element binding (CREB) protein pathway. These findings highlight a potential therapeutic target for the memory difficulties in AD.