Gabriela Mochol

Reward Learning Requires Activity of Matrix Metalloproteinase-9 in the Central Amygdala

Learning how to avoid danger and pursue reward depends on negative emotions motivating aversive learning and positive emotions motivating appetitive learning. The amygdala is a key component of the brain emotional system; however, an understanding of how various emotions are differentially processed in the amygdala has yet to be achieved. We report that matrix metalloproteinase-9 (MMP-9, extracellularly operating enzyme) in the central nucleus of the amygdala (CeA) is crucial for appetitive, but not for aversive, learning in mice. The knock-out of MMP-9 impairs appetitively motivated conditioning, but not an aversive one. MMP-9 is present at the excitatory synapses in the CeA with its activity greatly enhanced after the appetitive training. Finally, blocking extracellular MMP-9 activity with its inhibitor TIMP-1 provides evidence that local MMP-9 activity in the CeA is crucial for the appetitive, but not for aversive, learning.

Cognitive abilities of Alzheimer's disease transgenic mice are modulated by social context and circadian rhythm

In the present study, we used a new training paradigm in the intelliCage automatic behavioral assessment system to investigate cognitive functions of the transgenic mice harboring London mutation of the human amyloid precursor protein (APP.V717I). Three groups of animals: 5-, 12- and 18-24-month old were subjected to both Water Maze training and the IntelliCage-based appetitive conditioning. The spatial memory deficit was observed in all three groups of transgenic mice in both behavioral paradigms. However, the APP mice were capable to learn normally when co-housed with the wild-type (WT) littermates, in contrast to clearly impaired learning observed when the transgenic mice were housed alone. Furthermore, in the transgenic mice kept in the Intellicage alone, the cognitive deficit of the young animals was modulated by the circadian rhythm, namely was prominent only during the active phase of the day. The novel approach to study the transgenic mice cognitive abilities presented in this paper offers new insight into cognitive dysfunctions of the Alzheimers disease mouse model.

Variability of Visual Responses of Superior Colliculus Neurons Depends on Stimulus Velocity

Visually responding neurons in the superficial, retinorecipient layers of the cat superior colliculus receive input from two primarily parallel information processing channels, Y and W, which is reflected in their velocity response profiles. We quantified the time-dependent variability of responses of these neurons to stimuli moving with different velocities by Fano factor (FF) calculated in discrete time windows. The FF for cells responding to low-velocity stimuli, thus receiving W inputs, increased with the increase in the firing rate. In contrast, the dynamics of activity of the cells responding to fast moving stimuli, processed by Y pathway, correlated negatively with FF whether the response was excitatory or suppressive. These observations were tested against several types of surrogate data. Whereas Poisson description failed to reproduce the variability of all collicular responses, the inclusion of secondary structure to the generating point process recovered most of the observed features of responses to fast moving stimuli. Neither model could reproduce the variability of low-velocity responses, which suggests that, in this case, more complex time dependencies need to be taken into account. Our results indicate that Y and W channels may differ in reliability of responses to visual stimulation. Apart from previously reported morphological and physiological differences of the cells belonging to Y and W channels, this is a new feature distinguishing these two pathways.

Direct estimation of inhomogeneous markov interval models of spike trains

A necessary ingredient for a quantitative theory of neural coding is appropriate spike kinematics: a precise description of spike trains. While summarizing experiments by complete spike time collections is clearly inefficient and probably unnecessary, the most common probabilistic model used in neurophysiology, the inhomogeneous Poisson process, often seems too crude. Recently a more general model, the inhomogeneous Markov interval model (Berry & Meister, 1998; Kass & Ventura, 2001), was considered, which takes into account both the current experimental time and the time from the last spike. Several techniques were proposed to estimate the parameters of these models from data. Here we propose a direct method of estimation that is easy to implement, fast, and conceptually simple. The method is illustrated with an analysis of sample data from the cats superior colliculus.

Spectral Characteristics of Phase Sensitivity and Discharge Rate of Neurons in the Ascending Tectofugal Visual System

Drifting gratings can modulate the activity of visual neurons at the temporal frequency of the stimulus. In order to characterize the temporal frequency modulation in the cat’s ascending tectofugal visual system, we recorded the activity of single neurons in the superior colliculus, the suprageniculate nucleus, and the anterior ectosylvian cortex during visual stimulation with drifting sine-wave gratings. In response to such stimuli, neurons in each structure showed an increase in firing rate and/or oscillatory modulated firing at the temporal frequency of the stimulus (phase sensitivity). To obtain a more complete characterization of the neural responses in spatiotemporal frequency domain, we analyzed the mean firing rate and the strength of the oscillatory modulations measured by the standardized Fourier component of the response at the temporal frequency of the stimulus. We show that the spatiotemporal stimulus parameters that elicit maximal oscillations often differ from those that elicit a maximal discharge rate. Furthermore, the temporal modulation and discharge-rate spectral receptive fields often do not overlap, suggesting that the detection range for visual stimuli provided jointly by modulated and unmodulated response components is larger than the range provided by a one response component.

Cognitive abilities of Alzheimer transgenic mice as revealed by the IntelliCage system

Background: Treadmill gait analysis has been used to assess disease processes in a variety of different mouse models. Based on our observations, APP transgenic mice (Tg2576) move in ways much different than their wild-type (WT) littermates. To quantify these observations, we examined the time components of gait between age-matched Tg2576 and WT mice. However, body mass can play a role in the timing of gait so we compared a subset of two pairs of weight-matched 7 month old Tg2576 and WT mice to assess the effect of body mass as well. Methods: The Tg2576 mouse model has been shown to develop measurable plaque at about 9 months of age. Therefore, the two groups of mice were divided into three age categories; young (3-5 months old, Y), pre-plaque (6-8 months, PrP), and post-plaque (> 9 months, PoP). Gait data were gathered at a treadmill speed of 20 cm/sec. Videos were digitized (DigiGait, Mouse Specifics) and data analyzed by 2-way ANOVA with alpha 1⁄4 0.05. Variables measured included swing, break, propulsion, stance, and stride times as well as stride frequency. Results: A significant age by genotype interaction was found for swing (p 1⁄4 0.018), stance (0.049), and stride times (0.007) as well as stride frequency (0.031). Post-hoc analyses show that the greatest changes occurred in PrP-Tg2576 mice, which had significantly reduced times and increased stride frequency compared to PrP-WT; and the PoP-Tg2576 group, which were different from PoP-WT but not from YTg2576. The weight-matched Tg2576 had significantly lower swing and stride times and increased stride frequency compared to their WT counterparts. Conclusions: We found significant gait changes in the Tg2576 mouse model prior to expected plaque accumulation that are unlikely to be exclusively related to body mass. This may suggest that the Tg2576 model phenotype differs in more than just plaque accumulation. The small sample size may prove to be problematic. However, given the level of statistical significance for most of the variables, this preliminary study is likely to reflect a larger sample size.