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Fast spiking (FS) interneurons in the striatum are hypothesised to control spike timing in the numerous medium spiny (MS) projection neurons by inhibiting or delaying firing in the MS neurons. The FS neurons are connected to each other through electrical gap junctions. This might synchronise the FS neurons, leading to increased influence on target neurons. Here, we explore the possible difference between proximal and distal gap junction locations. Somatic and distal dendritic gap junctions with equal effective coupling coefficient, as defined for steady-state somatic inputs, showed significantly different effective coupling coefficient with transient inputs. However, the ability to synchronise spiking in pairwise coupled FS neurons, which received synaptic inputs as during striatal up-state periods, was as effective with distal gap junctions as with proximal ones. Proximal gap junctions, however, caused synchronisation within a more precise time window.

Striatum is the input stage of the basal ganglia, a collection of nuclei in the midbrain. The basal ganglia are involved in cognitive and motor behaviour, including reward-dependent learning. The reward system in the brain is heavily linked to the dopaminergic system, and many striatal neurons react in a reward-dependent manner. This study explores a minimal model of a striatal medium spiny (MS) projection neuron displaying dopamine-induced bistability. MS neurons mostly fluctuate between two states, a hyperpolarised down-state and a depolarised up-state. MS neurons are only active in the up-state and therefore spiking requires the transition from the down-state. For high dopamine levels in the model, the appearance of a bifurcation results in more distinct state transitions. GABAergic input from local fast-spiking interneurons to MS neurons results in a small depolarisation, but far from causing a transition to the up-state by itself. We investigate if a GABAergic PSP could facilitate the transition to the up-state elicited by glutamatergic input. The model predicts that GABAergic input to MS neurons might facilitate and speed up the transition to the up-state. The prerequisite for this is that the GABAergic enhancement starts slightly before the glutamatergic increase which causes the up-state transition.

Most computational models of the olfactory bulb are much smaller than any biological olfactory bulb-usually because the number of granule cells is much lower. The resulting subsampling of the inhibitory input may distort network dynamics and processing. We have constructed a large-scale model of the zebrafish olfactory bulb, as well as two smaller models, using the efficient parallellizing neural simulator SPLIT and data from a previously existing GENESIS model. We are studying several characteristics-among them overall behaviour, degree of synchrony of mitral cells and the timescale of appearance of synchrony-using cross-correlation plots and synthesized EEGs. Larger models with higher proportions of granule cells to mitral cells appear to give more synchronized output, especially for stimuli with shorter timescales.

We have developed a computational model of the regulation of @a- and @b-CaMKII activity, in order to examine (i) the importance of neighbour subunit interactions and (ii) the effect the higher CaMCa"4 affinity of @b-CaMKII has on the holoenzyme activity in different configurations with the same @a:@b ratio. The model consists of a deterministic biochemical network coupled to stochastic activation of CaMKII. The results suggest that CaMKII holoenzyme activity is non-linear and dependent on the holoenzyme configuration of isoforms. This is especially pronounced in situations with a high-dephosphorylation rate of CaMKII.

Striatal fast spiking (FS) interneurons provide inhibition to each other as well as to medium spiny projection (SP) neurons. They exhibit up-states synchronously with SP neurons, and receive GABAergic and AMPA synaptic input during both up- and down-states. The synaptic input during down-states can be considered noise and might affect detection of up-states. We investigate what role this background noise might play for up-state firing in a 127 compartment FS model neuron. The model has Na, KDr and KA conductances, and is activated through AMPA and GABA synapses. The model's response to current injection and synaptic inputs resembled experimental data. We show that intermediate levels of noise neither facilitates nor degrades the ability of the FS neuron model to detect up-states.

Slow Ca2+ oscillations caused by release from intracellular stores have been observed in neurons in the lamprey spinal cord. These oscillations are triggered by activation of metabotropic glutamate ...

A compartmental model of lamprey central pattern generator neurons was built in order to examine the effects of a fast, transient, high-voltage-activated potassium current (A-current) found experimentally. The model consisted of a soma, a compartment corresponding to the axon initial segment, and a dendritic tree. The simulation showed that the A-current was necessary for repetitive spiking in the single neuron following current injection. The functional role of adding an A-current was also examined in a network model. In this model, the A-current stabilizes the swimming rhythm by making the burst cycle duration and the number of spikes per burst less variable. All these effects are also seen experimentally.

Evidence suggests that protein kinase C (PKC) is required for long term memory storage such as classical conditioning. Stimulation of parallel fibers (PF) and climbing fibers (CF) of the cerebellum leads to production of the second messengers diacylglycerol, arachidonic acid, and calcium which are activators of PKC. A model is developed that describes the cascade of biochemical reactions in response to PF and CF stimulation and leading to PKC activation. Model simulations are used to evaluate the temporal specificity of PKC activation and the sensitivity of PKC activation to the interstimulus interval (ISI) of classical conditioning. Simulations at different ISI show that if PF stimulation precedes CF stimulation, PKC activation is elevated.

Factors controlling burst proportion in oscillatory networks are analyzed. This question is motivated by the lamprey swimming motor pattern which, independently on burst frequency, is characterized by a constant burst proportion. We investigate the effect of active modulation of the relative influence of a slower and faster adaptation controlling the depolarized phase. Using Morris–Lecar oscillators, NMDA-dependent oscillations or a network of mutually excitatory neurons, it is shown that the burst proportion can be controlled by increasing what corresponds to adaptation. Oscillations occur over an extended range of background stimulation values, leading to a higher maximal frequency.