Volume 13 Issue 10, October 2010

We often look back and forth between options before deciding which one to choose, even if we have seen them both before. A new study suggests that people are biased to choose things they look at more, providing new insight into how the subjective values of options are constructed.

Enhancers of endocannabinoid signaling are potential analgesics, but they cause unacceptable psychiatric side effects. A new study reports an inhibitor of endocannabinoid breakdown that has analgesic activity and cannot enter the CNS.

Stress primes the hypothalamic-pituitary-adrenal axis response to subsequent stressors. A new study finds that acute stress modifies the properties of excitatory synapses impinging on parvocellular neurons of the paraventricular nucleus.

Variation in neuronal properties is often thought of as noise that interferes with information processing. A study now suggests that neuronal diversity may actually improve the coding capacity of neural ensembles.

This review discusses the promises and pitfalls of animal models of psychiatric illnesses such as schizophrenia, bipolar disorder and depression. The authors propose guidelines for reporting and interpreting results from such models.

Degeneration of Purkinje neurons is the cause of ataxia in several neurodegenerative syndromes. Muguruma and colleagues describe a protocol for deriving Purkinje progenitors and neurons from mouse ES cells. Transplanted progenitors were able to integrate into the embryonic cerebellum with an efficiency of about 3% and adopt a Purkinje neuron phenotype.

Scott and colleagues show that expression of the transcription factor Sox9 is closely correlated with the transition from neuroepithelial cell to neural stem cell (NSC) during embryogenesis. Expression of Sox9 in early neuroepithelium elicited premature generation of NSCs. In the adult brain, Sox9 was necessary for the maintenance of NSCs and ependymal cells.

Fev is an ETS transcription factor essential for the generation of serotonin neurons. This study reports that ongoing Fev-directed transcription is required at different stages of life for multiple regulatory events that shape and maintain the serotonergic system. Furthermore, behavioral alterations can result from adult-onset perturbation of serotonergic transcription.

The authors find that the ATPase NSF interacts directly with Polo-like kinase 2 (Plk2), an activity-inducible kinase that is known to homeostatically decrease excitatory synapse number and strength. Plk2 disrupts the interaction between NSF and the GluA2 AMPAR subunit in a kinase-independent manner, promoting GluA2 internalization and decreased synaptic AMPAR current.

Segregating glutamate receptor trafficking function from the changes in synaptic spine morphology, this study finds that actin depolymerizing factor (ADF)- and cofilin-mediated actin dynamics control AMPAR trafficking during chemically induced long-term potentiation independent of actin's structural role.

This study finds that stimulation of muscarinic acetylcholine receptors causes long-term depression (LTD) of NMDA receptor–mediated synaptic transmission. This LTD requires the release of Ca²⁺ from IP₃-sensitive stores and involves an interaction between the Ca²⁺ sensor protein hippocalcin, the clathrin adaptor AP2 and NMDA receptors.

Glycine is a promiscuous neurotransmitter, as it acts primarily on the Cl-conducting, inhibitory glycine receptors (GlyRs), but it can also act as an allosteric modulator of excitatory NMDARs. Here, the authors found a reciprocal relation in glutamate and its analogs potentiating GlyR current in the rat spinal cord neurons.

The authors examine whether spinocerebellar neurons that convey proprioceptive sensory information also integrate information from cortical command systems by analyzing the circuitry and physiology of identified spinocerebellar tract neurons located in the Clarke's column of mouse spinal cord. They find that these neurons indeed nucleate spinal corollary circuits of relevance to motor planning and evaluation.

This study finds that the normal development of GABAergic feedforward inhibition in mouse layer 4 barrel cortex is disrupted by whisker trimming. Such sensory deprivation results in a weakened thalomocortical to feedforward interneuron connections and a lack of the normal reduction of the NMDA component of the thalamocortical input to excitatory cells, both of which are important for feedforward GABAergic inhibition.

The authors find that mutually exclusive splicing of the gene encoding the N-type Ca_v2.2 calcium channel is directly coupled to spinal morphine analgesia. The exon enriched in nociceptors promotes μ-opioid receptor–mediated inhibition of N-type channels by enhancing activity-independent inhibition. Spinal morphine analgesia is reduced in the absence of that exon.

A single exposure to a stressor is known to prime the hypothalamic-pituitary-adrenal axis to subsequent stressors. Kuzmiski et al. show that exposure to a stressor, via a corticotrophin-releasing hormone–dependent depression of postsynaptic NMDA receptors, enables glutamatergic synapses to undergo a short-term potentiation, manifested as an increase in presynaptic release probability.

The authors have developed a new inhibitor of the enzyme that degrades the endocannabinoid anandamide. This new drug does not cross the blood-brain barrier. It elevates peripheral anandamide only, which, acting on peripheral CB1 receptors, attenuates pain responses in rodents.

At chemical synapses, the dynamic membrane potential of a neuron must be converted into a train of spikes. Here, the authors conceptualize the neuron's efferent synapses as estimating the membrane potential trajectory from the spikes. They find that short-term changes in synaptic efficacy can be interpreted as implementing an optimal estimator.

Neurons of the same molecular type can have substantial differences in intrinsic properties. Here the authors find that intrinsic diversity in the mitral cells of the mouse olfactory bulb decreases the firing correlations between neurons and increases the amount of information that can be transmitted by the neuronal population.

The authors use combined electrostimulation, neurophysiology, microinjection and fMRI to show that stimulation of a site in the lateral geniculate nucleus of monkeys increases fMRI signals in regions of primary visual cortex, but suppresses it in retinotopically matched regions of extrastriate cortex. Their results suggest that electrostimulation disrupts cortico-cortical signal propagation by silencing the output of any neocortical area whose afferents are electrically stimulated.

To choose between two options, we often look repeatedly back and forth between them, presumably as a way of comparing their values. Here the authors propose a computational model of value-based decision making that can explain the relationship between fixation patterns and choices.