Research Article: Interplay between periodic stimulation and GABAergic inhibition in striatal network oscillations

Date Published: April 6, 2017

Publisher: Public Library of Science

Author(s): Jovana J. Belić, Arvind Kumar, Jeanette Hellgren Kotaleski, Stéphane Charpier.


Network oscillations are ubiquitous across many brain regions. In the basal ganglia, oscillations are also present at many levels and a wide range of characteristic frequencies have been reported to occur during both health and disease. The striatum, the main input nucleus of the basal ganglia, receives massive glutamatergic inputs from the cortex and is highly susceptible to external oscillations. However, there is limited knowledge about the exact nature of this routing process and therefore, it is of key importance to understand how time-dependent, external stimuli propagate through the striatal circuitry. Using a network model of the striatum and corticostriatal projections, we try to elucidate the importance of specific GABAergic neurons and their interactions in shaping striatal oscillatory activity. Here, we propose that fast-spiking interneurons can perform an important role in transferring cortical oscillations to the striatum especially to those medium spiny neurons that are not directly driven by the cortical oscillations. We show how the activity levels of different populations, the strengths of different inhibitory synapses, degree of outgoing projections of striatal cells, ongoing activity and synchronicity of inputs can influence network activity. These results suggest that the propagation of oscillatory inputs into the medium spiny neuron population is most efficient, if conveyed via the fast-spiking interneurons. Therefore, pharmaceuticals that target fast-spiking interneurons may provide a novel treatment for regaining the spectral characteristics of striatal activity that correspond to the healthy state.

Partial Text

The basal ganglia (BG) comprise the largest subcortical system in the brain and play a crucial role in motor control and cognitive processes [1–8]. Dysfunction of neural pathways between cortex and the BG circuitry is linked to many brain disorders, such as Parkinson’s disease (PD), L-DOPA-induced dyskinesia, Tourette’s syndrome, impulse control disorders, pathological gambling and Huntington’s disease [9–17]. The striatum is the largest and main input nucleus of the BG, receiving glutamatergic inputs from all cortical areas and thalamus [18–22]. About 95% of neurons in the striatum are medium spiny neurons (MSNs) that form the only output from the striatum [23–24]. Two of the most examined sources of GABAergic inhibition into MSNs are the feedback inhibition (FB) from the axon collaterals of the MSNs themselves, and the feedforward inhibition (FF) via the small population (1–2% of striatal neurons) of fast-spiking interneurons (FSIs) [25–28]. While feedback inhibition is made up of many weak inputs the feedforward inhibition is powerful, and spiking in a single FSI is capable of significantly delaying spike generation in a large number of postsynaptic medium spiny neurons [29–34]. High firing rate and uncorrelated spiking of FSIs may further amplify the effect of feedforward inhibition on the MSNs [35–36].

The striatum is a purely inhibitory recurrent network driven by excitatory inputs from the cortex and thalamus. An important feature of the striatum network is that the FF inhibition from FSIs to MSNs and FB inhibition from MSNs to other MSNs are clearly segregated. Individual striatal neurons do not act independently to affect rhythmic population activity, and here we use a spiking neuronal network model to study how they interact with each other and time-dependent external stimuli to induce oscillatory activity in the MSN population.

Oscillations are a ubiquitous feature of the population activity in the brain. Signatures of behavioral tasks and brain diseases (such as Parkinson’s disease) can be observed in the dynamics of oscillatory activity of the BG [37]. Therefore, there is a great interest in understanding the origin and modulation of oscillatory activity in the BG. While the mechanisms underlying the oscillatory activity of the subthalamic nucleus—globus pallidus (external segment) network are relatively well understood [59–61], the origin of oscillations in the striatum is poorly understood. Purely inhibitory networks such as the striatum can only generate oscillations when recurrent connectivity is dense and strong [40]. Therefore, it is likely that striatal oscillations are either generated by sub-threshold resonance of the striatal neurons or imposed by the cortico-thalamic projections. Here, we explored the later possibility and show that fast spiking interneurons could play a major role in transferring cortical oscillations to the striatal projection neurons.




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