Psychiatric disorders

Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex Covington, H. E. III et al. J. Neurosci. 31, 16082–16090 (2011)

Both reduced and increased activity in the prefrontal cortex (PFC) has been found in patients with depression. Here, the authors show reduced expression of several immediate early genes in the PFC in post-mortem tissue from depressed patients and in the medial PFC (mPFC) of mice exposed to chronic stress that showed depression-like behaviour, but not in mice that did not show effects of chronic stress exposure. Optogenetic mPFC stimulation in chronically stressed mice reversed depression-like — but not other — behaviours, suggesting that increasing overall PFC activity might have therapeutic potential.

Developmental neuroscience

TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons Baydyuk, M. et al. Proc. Natl Acad. Sci. USA 4 Jan 2011 (doi: 10.1073/pnas.1004744108)

In the peripheral nervous system, neurotrophins produced by target tissues regulate the size of the population of innervating neurons. Here, the authors show that neurotrophin signalling through the TrkB receptor is also important in the developing striatum, specifically for medium spiny neurons (MSNs), which project to the basal ganglia in a direct and an indirect pathway. Mice lacking striatal TrkB had a greatly reduced striatal volume, mainly owing to reduced survival of newborn MSNs destined for the indirect pathway. This shows that TrkB signalling has a crucial role in CNS development.

Place cells

Preplay of future place cell sequences by hippocampal cellular assemblies Dragoi, G. & Tonegawa, S. Nature 22 Dec 2010 (doi:10.1038/nature09633)

Hippocampal place cell firing shows 'replay' when an animal rests or sleeps following a novel environmental experience, which may reflect consolidation of the experienced environment. Here, Dragoi and Tonegawa show evidence of 'preplay': place cells that fired when a mouse explored a novel arm on a track also fired during the preceding rest period, in either a similar or reversed temporal sequence. The authors suggest that such preplay may organize hippocampal place cell assemblies to promote and accelerate the encoding of experiences in novel environments.

Neurodegenerative disease

Decreased clearance of CNS β-amyloid in Alzheimer's disease Mawuenyega, K. G. et al. Science 330, 1774 (2010)

According to the amyloid hypothesis of Alzheimer's disease, an imbalance between amyloid-β (Aβ) production and clearance underlies the disease. Mawuenyega et al. now show that this imbalance reflects dysregulation of Aβ clearance rather than of synthesis. They measured the production and clearance of Aβ40 and Aβ42 in the cerebrospinal fluid of patients with Alzheimer's disease and control subjects. The two groups had similar production rates for both peptides, but patients showed a 30% slower clearance of Aβ40 and Aβ42. These data support the hypothesis of impaired Aβ metabolism in Alzheimer's disease.