Inverse current source density method in two dimensions: inferring neural activation from multielectrode recordings.

The recent development of large multielectrode recording arrays has made it affordable for an increasing number of laboratories to record from multiple brain regions simultaneously. The development of analytical tools for array data, however, lags behind these technological advances in hardware. In this paper, we present a method based on forward modeling for estimating current source density from electrophysiological signals recorded on a two-dimensional grid using multi-electrode rectangular arrays. This new method, which we call two-dimensional inverse Current Source Density (iCSD 2D), is based upon and extends our previous one- and three-dimensional techniques. We test several variants of our method, both on surrogate data generated from a collection of Gaussian sources, and on model data from a population of layer 5 neocortical pyramidal neurons. We also apply the method to experimental data from the rat subiculum. The main advantages of the proposed method are the explicit specification of its assumptions, the possibility to include system-specific information as it becomes available, the ability to estimate CSD at the grid boundaries, and lower reconstruction errors when compared to the traditional approach. These features make iCSD 2D a substantial improvement over the approaches used so far and a powerful new tool for the analysis of multielectrode array data. We also provide a free GUI-based MATLAB toolbox to analyze and visualize our test data as well as user datasets.

Naturalistic stimulus trains evoke reproducible subicular responses both within and between animals in vivo.

Previous investigation of CA1-evoked subicular responses has used either single low-frequency pulses (LF), paired-pulses (PP), or high-frequency bursts. Here we test for the first time how subiculum responds to naturalistic stimulation trains (NSTs). We recorded CA1-evoked field potentials from dorsal rat subiculum in response to LF, PP, and two NST patterns. The latter were derived from CA1 place cell activity; NST1 contained bursts of stimuli presented in two main episodes, while the burst-patterned stimuli in NST2 were spaced more evenly. NSTs generated significantly greater field responses compared with LF or PP patterns. Response patterns to either NST were significantly correlated across trial repeats in 9 out of 10 rats, supporting a robust postsynaptic encoding of CA1 input by subiculum. Correlations between NST responses were also observed across experiments; however, these were more variable than those within experiments. The relationship between response magnitude and activation history revealed a strong correlation between magnitude and NST instantaneous frequency for NST1 but was weaker for NST2. In addition, the number of stimuli within a prior 500 ms window was a determining factor for response magnitude for both NSTs. Overall, the robust reproducibility in subicular responses within rats suggests that information within NSTs is faithfully transmitted through the CA1-subiculum axis. However, variation in response sequences across rats suggests that encoding patterns to the same input differ across the subiculum. Changes in the ratio of target bursting and regularly spiking neurons along the subicular proximodistal axis may account for this variation. The activation history of this connection also appears to be a strong determining factor for response magnitude.

Ultrasonic vocalisations explain unexpected effects on pre-pulse inhibition responses in rats chronically pre-treated with phencyclidine.

Deficits in pre-pulse inhibition (PPI-indicative of psychosis in humans) can be replicated in rats using the NMDA receptor antagonist phencyclidine (PCP). Ultrasonic vocalisations (USVs) produced by rats in response to acoustic startle are indicative of heightened anxiety; here we tested the predictive validity of USVs as an indicator of PPI. Male juvenile Sprague-Dawley rats (n=10) were treated for 14 days with either PCP (5mg/kg i.p.) or saline controls (1 ml/kg i.p.). PPI responses and USVs were recorded on days 16 and 19. PCP-treated rats showed decreased PPI performance on day 16 compared to controls; an observation that was unexpectedly reversed on day 19. Call parameters indicated that both treatment groups experienced similar levels of anxiety in response to the PPI paradigm on day 16. On day 19, the controls showed increased call duration and latency to onset (LtO) of calling, but decreased in the total number of calls produced compared to day 16. The calling period was significantly reduced compared to PCP-treated animals on say 19, whilst the LtO and duration were significantly increased. These changes were considered indicative of heightened levels of anxiety, most likely due to inadvertent fear conditioning (supported by reduced PPI performance) acquired during PPI testing. In contrast, the stability of USV characteristics emitted by PCP treated animals likely signified the detrimental effects of chronic PCP treatment on working memory. These results suggest that USVs are a valuable additional measure during PPI testing, helping to explain the unexpected results from our control group.

Neonatal maternal separation alters reward-related ultrasonic vocalizations in rat dams.

We examined the effects of brief or long durations of repeated maternal separation (MS) on ultrasonic vocalizations (USVs) in rat dams. 50-kHz USVs putatively identified as maternal in origin were emitted only immediately after pups were returned following MS. Maternal USV emission also depended on separation duration and pup age. Given that 50-kHz USVs are emitted in response to rewarding stimuli, MS may induce duration-dependent effects on maternal positive affect.