Cellular/Molecular
AGS-3 and RIC-8 Activate Gαo during Food Deprivation
Catherine Hofler and Michael R. Koelle
(see pages 11553–11562)
Many neurotransmitter receptors are coupled to G proteins, which have α, β, and γ subunits. Receptor activation causes exchange of GDP for GTP on Gα subunits, leading to dissociation of GTP-Gα from Gβγ subunits. These complexes activate separate signaling pathways until GTP is hydrolyzed, allowing GDP-Gα and Gβγ to reassociate. But if GDP-Gα instead associates with proteins containing G protein regulator (GPR) domains, the guanine nucleotide exchange factor Ric-8A can exchange GDP for GTP and prolong signaling. Hofler and Koelle suggest that this type of regulation allows Caenorhabditis elegans to adapt to reduced food supplies. Well-fed worms normally avoid octanol, but food-deprived worms do not. This behavioral switch results from activation of Gαo, which inhibits glutamate release from octanol-sensing neurons. This response requires the presence of RIC-8 and the GPR-domain protein AGS-3. Knocking out either AGS-3 or RIC-8 prevented reduction of octanol avoidance, but the effect was rescued by expression of constitutively active Gαo in octanol-sensing neurons.
Development/Plasticity/Repair
FAK Regulates Radial But Not Tangential Migration
Manuel Valiente, Gabriele Ciceri, Beatriz Rico, and Oscar Marín
(see pages 11678–11691)
Most cortical pyramidal cells are born in the ventricular zone and migrate outward along radial glia fibers toward the surface of the brain. This migration requires dynamic formation and disassembly of connexin-mediated adhesions between radial glia cells and neuronal somata and leading processes. Focal adhesion kinase (FAK) regulates the disassembly of adhesions during migration of non-neural cells, but its role in migrating neurons was unresolved. Valiente et al. report that loss of FAK function impaired radial migration of pyramidal neurons, causing them to assume an abnormal morphology suggestive of disrupted interaction with radial glia. FAK colocalized with connexin 26 in the perinuclear region and proximal swelling of the leading process of migrating neurons, and loss of FAK impaired the aggregation of connexin 26 in perinuclear puncta. In contrast, loss of FAK function did not disrupt migration of cortical interneurons, which migrate tangentially across the developing cortex independently of radial glial guides.
Behavioral/Systems/Cognitive
Habenula Inhibits Dopamine Neurons via Rostromedial Tegmental Nucleus
Simon Hong, Thomas C. Jhou, Mitchell Smith, Kadharbatcha S. Saleem, and Okihide Hikosaka
(see pages 11457–11471)
Goal-directed behaviors are shaped and maintained by the brain's reward circuitry, which comprises parts of prefrontal cortex, striatum, midbrain, and other structures. This circuitry enables an animal to use learned associations to predict the probability and quality of rewards based on present sensory cues, integrate this expectation with information about its current motivational state to choose an appropriate action, and evaluate the outcome of actions to shape future expectations. Reward evaluation depends on dopaminergic neurons in the substantia nigra pars compacta (SNc) that fire when a cue associated with reward appears. These neurons are inhibited upon stimulation of the lateral habenula, which contains neurons that fire in response to cues associated with no reward. The latter neurons are glutamatergic, however, and thus cannot directly inhibit SNc neurons. Results presented by Hong et al. strongly suggest that reward-related habenula neurons excite GABAergic neurons in the rostromedial tegmental nucleus, which in turn inhibit SNc neurons.
Neurobiology of Disease
Prenatal Stress Reduces Adult Mineralocorticoid Receptor Expression
Makoto Tamura, Mari Sajo, Akiyoshi Kakita, Norio Matsuki, and Ryuta Koyama
(see pages 11505–11514)
Chronic stress predisposes people toward depression, an effect that can be remarkably long-lasting. Children of women exposed to chronic stress during pregnancy are prone to depression into adulthood. This effect is probably mediated by corticosteroids, which are released in stressful situations, bind to receptors in the brain, and can cross the placental barrier. Tamura et al. show that subjecting pregnant rats to chronic stress caused adult offspring to exhibit depression-like behaviors. Dentate granule cells born on postnatal day 0 (P0) in rats exposed to prenatal stress (PS) had shorter, less-branched dendrites than controls at P60. In addition, evoked field EPSPs and long-term potentiation were reduced in adult PS rats. Observations in hippocampal slices indicated that PS slowed growth and increased retraction of dendrites for weeks after birth. The effects of PS were likely mediated by reduced expression of mineralocorticoid receptors. The effects were mimicked in culture by blocking these receptors and were attenuated by receptor agonists.
Tracings of dentate granule cells in P60 control rats (left) and rats born to mothers exposed to chronic stress during pregnancy (right). See the article by Tamura et al. for details.
