Faculty Bibliography

Applying past knowledge to future actions is crucial for adaptive choice behavior. Here, in this issue of Neuron, Donahue et al. (2013) show that reward enhances neural coding reliability for actions in a network of frontal and parietal brain areas.

Sparse Bayesian inference methods are applied to decode three-dimensional (3D) reach to grasp movement based on recordings of primary motor cortical (M1) ensembles from rhesus macaque. For three linear or nonlinear models tested, variational Bayes (VB) inference in combination with automatic relevance determination (ARD) is used for variable selection to avoid overfitting. The sparse Bayesian linear regression model achieved the overall best performance across objects and target locations. We assessed the sensitivity of M1 units in decoding and evaluated the proximal and distal representations of joint angles in population decoding. Our results suggest that the M1 ensembles recorded from the precentral gyrus area carry more proximal than distal information.

Genetic mutations causing human disease are conventionally thought to be inherited through the germ line from one's parents and present in all somatic (body) cells, except for most cancer mutations, which arise somatically. Increasingly, somatic mutations are being identified in diseases other than cancer, including neurodevelopmental diseases. Somatic mutations can arise during the course of prenatal brain development and cause neurological disease-even when present at low levels of mosaicism, for example-resulting in brain malformations associated with epilepsy and intellectual disability. Novel, highly sensitive technologies will allow more accurate evaluation of somatic mutations in neurodevelopmental disorders and during normal brain development.

Synfire chains are thought to underlie precisely timed sequences of spikes observed in various brain regions and across species. How they are formed is not understood. Here we analyze self-organization of synfire chains through the spike-timing dependent plasticity (STDP) of the synapses, axon remodeling, and potentiation decay of synaptic weights in networks of neurons driven by noisy external inputs and subject to dominant feedback inhibition. Potentiation decay is the gradual, activity-independent reduction of synaptic weights over time. We show that potentiation decay enables a dynamic and statistically stable network connectivity when neurons spike spontaneously. Periodic stimulation of a subset of neurons leads to formation of synfire chains through a random recruitment process, which terminates when the chain connects to itself and forms a loop. We demonstrate that chain length distributions depend on the potentiation decay. Fast potentiation decay leads to long chains with wide distributions, while slow potentiation decay leads to short chains with narrow distributions. We suggest that the potentiation decay, which corresponds to the decay of early long-term potentiation of synapses, is an important synaptic plasticity rule in regulating formation of neural circuity through STDP.

Inhibitory GABAergic interneurons have been extensively studied but their contribution to circuit dynamics remain poorly understood. Although it has been suggested that interneurons, especially those belonging to the same subclass, synchronize their activity and impart this synchrony onto their local network, recent theoretical and experimental work have challenged this view. To better understand the activity of interneurons during cortical activity, we combined molecular identification, two-photon imaging, and electrophysiological recordings in thalamocortical slices from mouse somatosensory cortex. Using calcium imaging to monitor cortical activity, we found low spiking correlations among parvalbumin or somatostatin interneurons during cortical UP states, indicating that interneurons do not synchronize their firing. Intracellular recordings confirmed that nearby interneurons do not display more synchronous spiking than excitatory cells. The lack of interneuron synchrony was also evident during slow oscillations, even among interneurons that were electrically coupled via gap junctions, suggesting that their coupling does not function to synchronize their activity. Using voltage-clamp recordings from nearby pyramidal cells, we found that inhibitory currents (IPSCs) are more correlated than excitatory ones, but that correlated IPSCs arise from the activation of common presynaptic inhibitory cells, rather than from synchronization of interneuron activity. Finally, we demonstrate that pharmacologically reducing inhibitory currents increases correlated excitatory activity. We conclude that inhibitory interneurons do not have synchronous activity during UP states, and that their function may be to decorrelate rather than to synchronize the firing of neurons within the local network.

BACKGROUND:Identifying variables that predict drug use in treatment-seeking drug addicted individuals is a crucial research and therapeutic goal. This study tested the hypothesis that choice to view cocaine images is associated with concurrent and prospective drug use in cocaine addiction. METHODS:To establish choice-concurrent drug use associations, 71 cocaine addicted subjects (43 current users and 28 treatment seekers) provided data on (A) choice to view cocaine images and affectively pleasant, unpleasant, and neutral images [collected under explicit contingencies (when choice was made between two fully visible side-by-side images) and under more probabilistic contingencies (when choice was made between pictures hidden under flipped-over cards)]; and (B) past-month cocaine and other drug use. To establish choice-prospective drug use associations, 20 of these treatment-seeking subjects were followed over the next 6 months. RESULTS:Baseline cocaine-related picture choice as measured by both tasks positively correlated with subjects' concurrent cocaine and other drug use as driven by the actively-using subjects. In a subsequent multiple regression analysis, choice to view cocaine images as compared with affectively pleasant images (under probabilistic contingencies) was the only predictor that continued to be significantly associated with drug use. Importantly, this same baseline cocaine>pleasant probabilistic choice also predicted the number of days drugs were used (cocaine, alcohol, and marijuana) over the next 6 months. CONCLUSIONS:Simulated cocaine choice - especially when probabilistic and when compared with other positive reinforcers - may provide a valid laboratory marker of current and future drug use in cocaine addiction.