Experience-dependent plasticity of visual cortical receptive fields (RFs) involves synaptic modifications in the underlying neural circuits, but the site and mechanism of these modifications remain to be elucidated. Using in vivo whole-cell recordings, we show that pairing visual stimulation at a given retinal location with spiking of a single neuron in developing rat visual cortex induces rapid RF modifications. The time course of the response to the visual stimulus at the paired RF location is altered, with an enhancement of the response preceding the spike time and a reduction following the spike. Such bidirectional modification is consistent with spike timing-dependent plasticity. Response modification also occurs at nearby locations, the direction and magnitude of which are correlated with the change at the paired location. In addition, changes at unpaired locations show a negative correlation with the initial strength of the response, which may facilitate rapid modification of the spatial RF profile.

A hybrid protein, tPA/GFP, consisting of rat tissue plasminogen activator (tPA) and green fluorescent protein (GFP) was expressed in PC12 cells and used to study the distribution, secretory behavior, and dynamics of secretory granules containing tPA in living cells with a neuronal phenotype. High-resolution images demonstrate that tPA/GFP has a growth cone-biased distribution in differentiated cells and that tPA/GFP is transported in granules of the regulated secretory pathway that colocalize with granules containing secretogranin II. Time-lapse images of secretion reveal that secretagogues induce substantial loss of cellular tPA/GFP fluorescence, most importantly from growth cones. Time-lapse images of the axonal transport of granules containing tPA/GFP reveal a surprising complexity to granule dynamics. Some granules undergo canonical fast axonal transport; others move somewhat more slowly, especially in highly fluorescent neurites. Most strikingly, granules traffic bidirectionally along neurites to an extent that depends on granule accumulation, and individual granules can reverse their direction of motion. The retrograde component of this bidirectional transport may help to maintain cellular homeostasis by transporting excess tPA/GFP back toward the cell body. The results presented here provide a novel view of the axonal transport of secretory granules. In addition, the results suggest that tPA is targeted for regulated secretion from growth cones of differentiated cells, strategically positioning tPA to degrade extracellular barriers or to activate other barrier-degrading proteases during axonal elongation.

The ability to recognize auditory objects like words and bird songs is thought to depend on neural responses that are selective between categories of the objects and tolerant of variation within those categories. To determine whether a hierarchy of increasing selectivity and tolerance exists in the avian auditory system, we trained European starlings (Sturnus vulgaris) to differentially recognize sets of songs, then measured extracellular single unit responses under urethane anesthesia in six areas of the auditory cortex. Responses were analyzed with a novel, generalized linear mixed model that provides robust estimates of the variance in responses to different stimuli. There were significant differences between areas in selectivity, tolerance, and the effects of training. The L2b and L1 subdivisions of field L had the least selectivity and tolerance. The caudal nidopallium (NCM) and subdivision L3 of field L were more selective than other areas, whereas the medial and lateral mesopallium (CMM and CLM) were more tolerant than NCM or L2b. L3 had a multimodal distribution of tolerance. Sensitivity to songs that were familiar and those that were not also distinguished the responses of CMM and NCM. There were significant differences across areas between neurons with wide and narrow spikes. Collectively these results do not fit the traditional hierarchical view of the avian auditory forebrain, but are consistent with emerging concepts homologizing avian cortical and neocortical circuitry. The results suggest a functional divergence within the cortex into processing streams that respond to complementary aspects of the variability in communicative sounds.

Recent results demonstrate techniques for fully quantitative, statistical inference of the dynamics of individual neurons under the Hodgkin-Huxley framework of voltage-gated conductances. Using a variational approximation, this approach has been successfully applied to simulated data from model neurons. Here, we use this method to analyze a population of real neurons recorded in a slice preparation of the zebra finch forebrain nucleus HVC. Our results demonstrate that using only 1,500 ms of voltage recorded while injecting a complex current waveform, we can estimate the values of 12 state variables and 72 parameters in a dynamical model, such that the model accurately predicts the responses of the neuron to novel injected currents. A less complex model produced consistently worse predictions, indicating that the additional currents contribute significantly to the dynamics of these neurons. Preliminary results indicate some differences in the channel complement of the models for different classes of HVC neurons, which accords with expectations from the biology. Whereas the model for each cell is incomplete (representing only the somatic compartment, and likely to be missing classes of channels that the real neurons possess), our approach opens the possibility to investigate in modeling the plausibility of additional classes of channels the cell might possess, thus improving the models over time. These results provide an important foundational basis for building biologically realistic network models, such as the one in HVC that contributes to the process of song production and developmental vocal learning in songbirds.