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Interplay between periodic stimulation and GABAergic inhibition in striatal network oscillations

View Article: PubMed Central - PubMed

ABSTRACT

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.

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Sensitivity of the oscillations in the MSN population to the parameters of the FF inhibition.(A) Increase in the strength of FF inhibition enhanced the transfer of oscillations from FSIs to MSNs as indicated by a monotonic increase in the OI of MSNs. (B) OI of MSNs also monotonically increased as a fraction of stimulated FSIs increased. (C) Influence of the background activity in unstimulated FSIs (those that did not receive any sinusoidal inputs) on the transfer of oscillations to the MSN population. Maximal amplitude of the oscillatory inputs was equal to 350 pA (mean ± std firing of FSIs was equal to 30.98 ± 4.2 Hz) and was kept constant throughout all simulations.
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pone.0175135.g005: Sensitivity of the oscillations in the MSN population to the parameters of the FF inhibition.(A) Increase in the strength of FF inhibition enhanced the transfer of oscillations from FSIs to MSNs as indicated by a monotonic increase in the OI of MSNs. (B) OI of MSNs also monotonically increased as a fraction of stimulated FSIs increased. (C) Influence of the background activity in unstimulated FSIs (those that did not receive any sinusoidal inputs) on the transfer of oscillations to the MSN population. Maximal amplitude of the oscillatory inputs was equal to 350 pA (mean ± std firing of FSIs was equal to 30.98 ± 4.2 Hz) and was kept constant throughout all simulations.

Mentions: In our model, cortical oscillations are first transferred to the FSI activity and then imprinted on to the activity of MSNs. That is, once oscillations are established in FSIs, e.g. by increasing the drive to FSIs, the transmission of the oscillations depends on the effective FSIs inputs to the MSNs. The effective FSIs input to MSNs in turns depends on the number of FSIs inputs to individual MSNs, strength of FF inhibition (JFFinh), and area of the IPSP. Indeed, increasing the strength of the FF inhibition (JFFinh) increased the OI (Fig 5A). A similar effect would be observed if we changed the connection probability between FSIs and MSNs (data not shown). For the specific choice of JFFinh, connection probability and cortical input drive (Amax) within a physiologic range, oscillations could be transferred to MSNs when as little as 16 FSIs (28% of the local FSI population) were driven by cortical inputs (Fig 5B). The maximum amplitude of the oscillatory inputs (Amax) was set to 350 pA (mean ± std firing of FSIs was equal to 30.98 ± 4.2 Hz) and was kept constant throughout all simulations. When only a fraction of FSIs were stimulated the irregular spiking activity of unstimulated FSIs could slightly impair the transmission of oscillations by adding noise to the oscillatory FSIs inputs to MSNs. Fig 5C shows that when 36 FSIs received oscillatory input on the top of the Poisson background activity (see Materials and methods), and the rest of the FSIs received only Poisson drive that made them fire at two different frequencies, ~20 Hz and ~80 Hz, respectively. In the latter case, the peak was smaller but not significantly (0.033 vs 0.028, p = 0.017).


Interplay between periodic stimulation and GABAergic inhibition in striatal network oscillations
Sensitivity of the oscillations in the MSN population to the parameters of the FF inhibition.(A) Increase in the strength of FF inhibition enhanced the transfer of oscillations from FSIs to MSNs as indicated by a monotonic increase in the OI of MSNs. (B) OI of MSNs also monotonically increased as a fraction of stimulated FSIs increased. (C) Influence of the background activity in unstimulated FSIs (those that did not receive any sinusoidal inputs) on the transfer of oscillations to the MSN population. Maximal amplitude of the oscillatory inputs was equal to 350 pA (mean ± std firing of FSIs was equal to 30.98 ± 4.2 Hz) and was kept constant throughout all simulations.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5383243&req=5

pone.0175135.g005: Sensitivity of the oscillations in the MSN population to the parameters of the FF inhibition.(A) Increase in the strength of FF inhibition enhanced the transfer of oscillations from FSIs to MSNs as indicated by a monotonic increase in the OI of MSNs. (B) OI of MSNs also monotonically increased as a fraction of stimulated FSIs increased. (C) Influence of the background activity in unstimulated FSIs (those that did not receive any sinusoidal inputs) on the transfer of oscillations to the MSN population. Maximal amplitude of the oscillatory inputs was equal to 350 pA (mean ± std firing of FSIs was equal to 30.98 ± 4.2 Hz) and was kept constant throughout all simulations.
Mentions: In our model, cortical oscillations are first transferred to the FSI activity and then imprinted on to the activity of MSNs. That is, once oscillations are established in FSIs, e.g. by increasing the drive to FSIs, the transmission of the oscillations depends on the effective FSIs inputs to the MSNs. The effective FSIs input to MSNs in turns depends on the number of FSIs inputs to individual MSNs, strength of FF inhibition (JFFinh), and area of the IPSP. Indeed, increasing the strength of the FF inhibition (JFFinh) increased the OI (Fig 5A). A similar effect would be observed if we changed the connection probability between FSIs and MSNs (data not shown). For the specific choice of JFFinh, connection probability and cortical input drive (Amax) within a physiologic range, oscillations could be transferred to MSNs when as little as 16 FSIs (28% of the local FSI population) were driven by cortical inputs (Fig 5B). The maximum amplitude of the oscillatory inputs (Amax) was set to 350 pA (mean ± std firing of FSIs was equal to 30.98 ± 4.2 Hz) and was kept constant throughout all simulations. When only a fraction of FSIs were stimulated the irregular spiking activity of unstimulated FSIs could slightly impair the transmission of oscillations by adding noise to the oscillatory FSIs inputs to MSNs. Fig 5C shows that when 36 FSIs received oscillatory input on the top of the Poisson background activity (see Materials and methods), and the rest of the FSIs received only Poisson drive that made them fire at two different frequencies, ~20 Hz and ~80 Hz, respectively. In the latter case, the peak was smaller but not significantly (0.033 vs 0.028, p = 0.017).

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus