Wild oscillations in a nonlinear neuron model with resets: (II) Mixed-mode oscillations

This work continues the analysis of complex dynamics in a class of bidimensional nonlinear hybrid dynamical systems with resets modeling neuronal voltage dynamics with adaptation and spike emission. We show that these models can generically display a form of mixed-mode oscillations (MMOs), which are trajectories featuring an alternation of small oscillations with spikes or bursts (multiple consecutive spikes). The mechanism by which these are generated relies fundamentally on the hybrid structure of the flow: invariant manifolds of the continuous dynamics govern small oscillations, while discrete resets govern the emission of spikes or bursts, contrasting with classical MMO mechanisms in ordinary differential equations involving more than three dimensions and generally relying on a timescale separation. The decomposition of mechanisms reveals the geometrical origin of MMOs, allowing a relatively simple classification of points on the reset manifold associated to specific numbers of small oscillations. We show that the MMO pattern can be described through the study of orbits of a discrete adaptation map, which is singular as it features discrete discontinuities with unbounded left- and right-derivatives. We study orbits of the map via rotation theory for discontinuous circle maps and elucidate in detail complex behaviors arising in the case where MMOs display at most one small oscillation between each consecutive pair of spikes

Correlation transfer from basal ganglia to thalamus in Parkinson's disease

Spike trains from neurons in the basal ganglia of parkinsonian primates show increased pairwise correlations, oscillatory activity, and burst rate compared to those from neurons recorded during normal brain activity. However, it is not known how these changes affect the behavior of downstream thalamic neurons. To understand how patterns of basal ganglia population activity may affect thalamic spike statistics, we study pairs of model thalamocortical (TC) relay neurons receiving correlated inhibitory input from the internal segment of the globus pallidus (GPi), a primary output nucleus of the basal ganglia. We observe that the strength of correlations of TC neuron spike trains increases with the GPi correlation level, and bursty firing patterns such as those seen in the parkinsonian GPi allow for stronger transfer of correlations than do firing patterns found under normal conditions. We also show that the T-current in the TC neurons does not significantly affect correlation transfer, despite its pronounced effects on spiking. Oscillatory firing patterns in GPi are shown to affect the timescale at which correlations are best transferred through the system. To explain this last result, we analytically compute the spike count correlation coefficient for oscillatory cases in a reduced point process model. Our analysis indicates that the dependence of the timescale of correlation transfer is robust to different levels of input spike and rate correlations and arises due to differences in instantaneous spike correlations, even when the long timescale rhythmic modulations of neurons are identical. Overall, these results show that parkinsonian firing patterns in GPi do affect the transfer of correlations to the thalamus

The Interaction of Intrinsic Dynamics and Network Topology in Determining Network Burst Synchrony

The pre-Bötzinger complex (pre-BötC), within the mammalian respiratory brainstem, represents an ideal system for investigating the synchronization properties of complex neuronal circuits via the interaction of cell-type heterogeneity and network connectivity. In isolation, individual respiratory neurons from the pre-BötC may be tonically active, rhythmically bursting, or quiescent. Despite this intrinsic heterogeneity, coupled networks of pre-BötC neurons en bloc engage in synchronized bursting that can drive inspiratory motor neuron activation. The region's connection topology has been recently characterized and features dense clusters of cells with occasional connections between clusters. We investigate how the dynamics of individual neurons (quiescent/bursting/tonic) and the betweenness centrality of neurons’ positions within the network connectivity graph interact to govern network burst synchrony, by simulating heterogeneous networks of computational model pre-BötC neurons. Furthermore, we compare the prevalence and synchrony of bursting across networks constructed with a variety of connection topologies, analyzing the same collection of heterogeneous neurons in small-world, scale-free, random, and regularly structured networks. We find that several measures of network burst synchronization are determined by interactions of network topology with the intrinsic dynamics of neurons at central network positions and by the strengths of synaptic connections between neurons. Surprisingly, despite the functional role of synchronized bursting within the pre-BötC, we find that synchronized network bursting is generally weakest when we use its specific connection topology, which leads to synchrony within clusters but poor coordination across clusters. Overall, our results highlight the relevance of interactions between topology and intrinsic dynamics in shaping the activity of networks and the concerted effects of connectivity patterns and dynamic heterogeneities

Tailoring inputs to achieve maximal neuronal firing

We consider the constrained optimization of excitatory synaptic input patterns to maximize spike generation in leaky integrate-and-fire (LIF) and theta model neurons. In the case of discrete input kicks with a fixed total magnitude, optimal input timings and strengths are identified for each model using phase plane arguments. In both cases, optimal features relate to finding an input level at which the drop in input between successive spikes is minimized. A bounded minimizing level always exists in the theta model and may or may not exist in the LIF model, depending on parameter tuning. We also provide analytical formulas to estimate the number of spikes resulting from a given input train. In a second case of continuous inputs of fixed total magnitude, we analyze the tuning of an input shape parameter to maximize the number of spikes occurring in a fixed time interval. Results are obtained using numerical solution of a variational boundary value problem that we derive, as well as analysis, for the theta model and using a combination of simulation and analysis for the LIF model. In particular, consistent with the discrete case, the number of spikes in the theta model rises and then falls again as the input becomes more tightly peaked. Under a similar variation in the LIF case, we numerically show that the number of spikes increases monotonically up to some bound and we analytically constrain the times at which spikes can occur and estimate the bound on the number of spikes fired

Gasoline Consumption Attributable to Gasoline Powered Watercraft Use in Maine

This report, the third of three, presents the results of a survey of gasoline powered watercraft users whose watercraft were registered in the State of Maine during 2001

Synchronization hubs may arise from strong rhythmic inhibition during gamma oscillations in primary visual cortex

Poster presentation from Twentieth Annual Computational Neuroscience Meeting: CNS*2011 Stockholm, Sweden. 23-28 July 2011. Parallel multiunit recordings from V1 in anesthetized cat were collected during the presentation of random sequences of drifting sinusoidal gratings at 12 fixed orientations while gamma oscillations were present. In agreement with the seminal work [1], most units were orientation selective to varying degrees and synchronization was evident in spike train crosscorrelograms computed between units with similar preferred orientations, particularly during the presentation of optimal stimuli. Interestingly, a subset of units, which we refer to as synchronization hubs, were additionally found to synchronize with units having differing preferred orientations which was consistent with a previous study [2]. Moreover, oscillatory patterning in spike train autocorrelograms was also found to be strongest in units denoted as synchronization hubs, and synchronization hubs also tended to have narrower tuning curves relative to other units. We used simplified computational models of small networks of V1 neurons to demonstrate that neurons subject to a sufficiently strong level of inhibitory input can function as synchronization hubs. Neurons were endowed either with integrate-and-fire or conductance-based dynamics and each neuron received a combination of excitatory (AMPA) synaptic inputs that were Poisson-distributed and inhibitory (GABA) inputs that were coherent at a gamma-frequency range. If the strength of rhythmic inhibition was increased for a subset of neurons in the network, and excitation was increased simultaneously to maintain a fixed firing rate, then these neurons produced stronger oscillatory patterning in their discharge probabilities. The oscillations in turn synchronized these neurons with other neurons in the network. Importantly, the strength of synchronization increased with neurons of differing orientation preferences even though no direct synaptic coupling existed between the hubs and the other neurons. Enhanced levels of inhibition account for the emergence of synchronization hubs in the following way: Inhibitory inputs exhibiting a gamma rhythm determine a time window within which a cell is likely to discharge. Increased levels of inhibition narrow down this window further simultaneously leading to (i) even stronger oscillatory patterning of the neuron's activity and (ii) enhanced synchronization with other neurons. This enables synchronization even between cells with differing orientation preferences. Additionally, the same increased levels of inhibition may be responsible for the narrow tuning curves of hub neurons. In conclusion, synchronization hubs may be the cells that interact most strongly with the network of inhibitory interneurons during gamma oscillations in primary visual cortex

Paying Our Dues: The Role of Professional Societies in the Evolution of Mathematical Biology Education.

Mathematical biology education provides key foundational underpinnings for the scholarly work of mathematical biology. Professional societies support such education efforts via funding, public speaking opportunities, Web presence, publishing, workshops, prizes, opportunities to discuss curriculum design, and support of mentorship and other means of sustained communication among communities of scholars. Such programs have been critical to the broad expansion of the range and visibility of research and educational activities in mathematical biology. We review these efforts, past and present, across multiple societies-the Society for Mathematical Biology (SMB), the Symposium on Biomathematics and Ecology Education and Research (BEER), the Mathematical Association of America (MAA), and the Society for Industrial and Applied Mathematics (SIAM). We then proceed to suggest ways that professional societies can serve as advocates and community builders for mathematical biologists at all levels, noting that education continues throughout a career and also emphasizing the value of educating new generations of students. Our suggestions include collecting and disseminating data related to biomath education; developing and maintaining mentoring systems and research communities; and providing incentives and visibility for educational efforts within mathematical biology