The Long-Term Structural Plasticity of Cerebellar Parallel Fiber Axons and Its Modulation by Motor Learning.

The Long-term Structural Plasticity of Cerebellar Parallel Fiber Axons and Its Modulation by Motor Learning.

J Neurosci. 2013 May 8; 33(19): 8301-7
Carrillo J, Cheng SY, Ko KW, Jones TA, Nishiyama H

Presynaptic axonal varicosities, like postsynaptic spines, are dynamically added and eliminated even in mature neuronal circuitry. To study the role of this axonal structural plasticity in behavioral learning, we performed two-photon in vivo imaging of cerebellar parallel fibers (PFs) in adult mice. PFs make excitatory synapses on Purkinje cells (PCs) in the cerebellar cortex, and long-term potentiation and depression at PF-PC synapses are thought to play crucial roles in cerebellar-dependent learning. Time-lapse vital imaging of PFs revealed that, under a control condition (no behavioral training), ?10% of PF varicosities appeared and disappeared over a period of 2 weeks without changing the total number of varicosities. The fraction of dynamic PF varicosities significantly diminished during training on an acrobatic motor skill learning task, largely because of reduced addition of new varicosities. Thus, this form of motor learning was associated with greater structural stability of PFs and a slight decrease in the total number of varicosities. Together with prior findings that the number of PF-PC synapses increases during similar training, our results suggest that acrobatic motor skill learning involves a reduction of some PF inputs and a strengthening of others, probably via the conversion of some preexisting PF varicosities into multisynaptic terminals. HubMed – depression


Serotonin is required for exercise-induced adult hippocampal neurogenesis.

J Neurosci. 2013 May 8; 33(19): 8270-5
Klempin F, Beis D, Mosienko V, Kempermann G, Bader M, Alenina N

Voluntary wheel running has long been known to induce precursor cell proliferation in adult hippocampal neurogenesis in rodents. However, mechanisms that couple activity with the promitotic effect are not yet fully understood. Using tryptophan hydroxylase (TPH) 2 deficient (Tph2-deficient) mice that lack brain serotonin, we explored the relationship between serotonin signaling and exercise-induced neurogenesis. Surprisingly, Tph2-deficient mice exhibit normal baseline hippocampal neurogenesis but impaired activity-induced proliferation. Our data demonstrate that the proproliferative effect of running requires the release of central serotonin in young-adult and aged mice. Lack of brain serotonin further results in alterations at the stage of Sox2-positive precursor cells, suggesting physiological adaptations to changes in serotonin supply to maintain homeostasis in the neurogenic niche. We conclude that serotonin plays a direct and acute regulatory role in activity-dependent hippocampal neurogenesis. The understanding of exercise-induced neurogenesis might offer preventive but also therapeutic opportunities in depression and age-related cognitive decline. HubMed – depression



Depress Anxiety. 2013 May 8;
Bennett K, Manassis K, Walter SD, Cheung A, Wilansky-Traynor P, Diaz-Granados N, Duda S, Rice M, Baer S, Barrett P, Bodden D, Cobham VE, Dadds MR, Flannery-Schroeder E, Ginsburg G, Heyne D, Hudson JL, Kendall PC, Liber J, Warner CM, Mendlowitz S, Nauta MH, Rapee RM, Silverman W, Siqueland L, Spence SH, Utens E, Wood JJ

BACKGROUND: Investigations of age effects on youth anxiety outcomes in randomized trials (RCTs) of cognitive behavior therapy (CBT) have failed to yield a clear result due to inadequate statistical power and methodologic weaknesses. We conducted an individual patient data metaanalysis to address this gap. QUESTION: Does age moderate CBT effect size, measured by a clinically and statistically significant interaction between age and CBT exposure? METHODS: All English language RCTs of CBT for anxiety in 6-19 year olds were identified using systematic review methods. Investigators of eligible trials were invited to submit their individual patient data. The anxiety disorder interview schedule (ADIS) primary diagnosis severity score was the primary outcome. Age effects were investigated using multilevel modeling to account for study level data clustering and random effects. RESULTS: Data from 17 of 23 eligible trials were obtained (74%); 16 studies and 1,171 (78%) cases were available for the analysis. No interaction between age and CBT exposure was found in a model containing age, sex, ADIS baseline severity score, and comorbid depression diagnosis (power ? 80%). Sensitivity analyses, including modeling age as both a categorical and continuous variable, revealed this result was robust. CONCLUSIONS: Adolescents who receive CBT in efficacy research studies show benefits comparable to younger children. However, CBT protocol modifications routinely carried out by expert trial therapists may explain these findings. Adolescent CBT protocols are needed to facilitate the transportability of efficacy research effects to usual care settings where therapists may have less opportunity for CBT training and expertise development. HubMed – depression


Association analysis between the A118G polymorphism in the OPRM1 gene and treatment response to venlafaxine XR in generalized anxiety disorder.

Hum Psychopharmacol. 2013 May 8;
Cooper AJ, Rickels K, Lohoff FW

Patients diagnosed with generalized anxiety disorder (GAD) exhibit differential responses to standard antidepressant pharmacotherapy. Mounting evidence demonstrates that genetic differences may be implicated in treatment response in disorders like GAD. In this study, we examined whether the OPRM1 gene, which has been implicated in antidepressant treatment response in major depressive disorder, also has an effect in GAD. In our study, 156 patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study. Genotypes were obtained for the OPRM1 functional variant A118G for the entire sample (n?=?151); however, only the European American population was considered (n?=?108) for pharmacogenetic analysis. We found no significant association between A118G and antidepressant treatment response in our GAD population. Future studies that include different single nucleotide polymorphisms of the OPRM1 gene as well as larger populations will need to be conducted to further elucidate the pharmacogenetic role of the endogenous opioid system in anxiety disorders. Copyright © 2013 John Wiley & Sons, Ltd. HubMed – depression