Selective optogenetic drive of fast-spiking (FS) interneurons (INs) leads to enhanced local field potential (LFP) power across the traditional "gamma" frequency band (20-80 Hz; Cardin et al., 2009). In contrast, drive to regular-spiking (RS) pyramidal cells enhances power at lower frequencies, with a peak at 8 Hz. The first result is consistent with previous computational studies emphasizing the role of FS and the time constant of GABA(A) synaptic inhibition in gamma rhythmicity. However, the same theoretical models do not typically predict low-frequency LFP enhancement with RS drive. To develop hypotheses as to how the same network can support these contrasting behaviors, we constructed a biophysically principled network model of primary somatosensory neocortex containing FS, RS, and low-threshold spiking (LTS) INs. Cells were modeled with detailed cell anatomy and physiology, multiple dendritic compartments, and included active somatic and dendritic ionic currents. Consistent with prior studies, the model demonstrated gamma resonance during FS drive, dependent on the time constant of GABA(A) inhibition induced by synchronous FS activity. Lower-frequency enhancement during RS drive was replicated only on inclusion of an inhibitory LTS population, whose activation was critically dependent on RS synchrony and evoked longer-lasting inhibition. Our results predict that differential recruitment of FS and LTS inhibitory populations is essential to the observed cortical dynamics and may provide a means for amplifying the natural expression of distinct oscillations in normal cortical processing.
"Excitatory PY cells corresponded to regular spiking PY cells, while I cells corresponded to fast-spiking interneurons. Low-threshold spiking interneurons were not included, as they are believed to contribute to lowfrequency rhythmogenesis (Fanselow et al. 2008; Vierling-Claassen et al. 2010). The neurons were modeled using single-compartment Hodgkin-Huxley type dynamics, modified by Av-Ron (1994). "
[Show abstract][Hide abstract] ABSTRACT: High-gamma activity, ranging in frequency between approximately 60 Hz and 200 Hz, has been observed in LFP, ECoG, EEG and MEG signals during cortical activation, in a variety of functional brain systems. The origin of these signals is yet unknown. Using computational modeling we show that a cortical network model receiving thalamic input generates high-gamma responses comparable to those observed in LFP recorded in monkey somatosensory cortex during vibrotactile stimulation. These high-gamma oscillations appear to be mediated mostly by an excited population of inhibitory fast-spiking interneurons firing at high-gamma frequencies and pacing excitatory regular-spiking pyramidal cells, which fire at lower rates but in phase with the population rhythm. The physiological correlates of high-gamma activity, in this model of local cortical circuits, appear to be similar to those proposed for hippocampal ripples generated by subsets of interneurons that regulate the discharge of principal cells.
Journal of Neurophysiology 09/2014; DOI:10.1152/jn.00844.2013 · 2.89 Impact Factor
"These oscillations are thought to reflect synchronous activity of rhythmically firing neurons (Jensen et al., 2007). Activity of PV/FS interneurons has been found in several studies, both experimental and computational, to have a significant role in maintaining the above oscillations and neuronal synchronization (Borgers et al., 2008; Cardin et al., 2009; Sohal et al., 2009; Vierling-Claassen et al., 2010). "
[Show abstract][Hide abstract] ABSTRACT: Neocortical network activity is generated through a dynamic balance between excitation, provided by pyramidal neurons, and inhibition, provided by interneurons. Imbalance of the excitation/inhibition ratio has been identified in several neuropsychiatric diseases, such as schizophrenia, autism and epilepsy, which also present with other cognitive deficits and symptoms associated with prefrontal cortical (PFC) dysfunction. We undertook a computational approach to study how changes in the excitation/inhibition balance in a PFC microcircuit model affect the properties of persistent activity, considered the cellular correlate of working memory function in PFC. To this end, we constructed a PFC microcircuit, consisting of pyramidal neuron models and all three different interneuron types: fast-spiking (FS), regular-spiking (RS), and irregular-spiking (IS) interneurons. Persistent activity was induced in the microcircuit model with a stimulus to the proximal apical dendrites of the pyramidal neuron models, and its properties were analyzed, such as the induction profile, the interspike intervals (ISIs) and neuronal synchronicity. Our simulations showed that (a) the induction but not the firing frequency or neuronal synchronicity is modulated by changes in the NMDA-to-AMPA ratio on FS interneuron model, (b) removing or decreasing the FS model input to the pyramidal neuron models greatly limited the biophysical modulation of persistent activity induction, decreased the ISIs and neuronal synchronicity during persistent activity, (c) the induction and firing properties could not be altered by the addition of other inhibitory inputs to the soma (from RS or IS models), and (d) the synchronicity change could be reversed by the addition of other inhibitory inputs to the soma, but beyond the levels of the control network. Thus, generic somatic inhibition acts as a pacemaker of persistent activity and FS specific inhibition modulates the output of the pacemaker.
"Spike times were recorded for all cell types, as well as somatic current contributions from GABA A -mediated synapses onto pyramidal cell somata using NEURON's built-in routines. Spectrograms were calculated using a Morlet wavelet method as previously described in Jones et al. (2009); Vierling-Claassen et al. (2010) over a frequency range of 1–150 Hz. Units of Morlet power (P M ) are (nAm) 2 . "
[Show abstract][Hide abstract] ABSTRACT: Gamma frequency rhythms have been implicated in numerous studies for their role in healthy and abnormal brain function. The frequency band has been described to encompass as broad a range as 30-150 Hz. Crucial to understanding the role of gamma in brain function is an identification of the underlying neural mechanisms, which is particularly difficult in the absence of invasive recordings in macroscopic human signals such as those from magnetoencephalography (MEG) and electroencephalography (EEG). Here, we studied features of current dipole (CD) signals from two distinct mechanisms of gamma generation, using a computational model of a laminar cortical circuit designed specifically to simulate CDs in a biophysically principled manner (Jones et al., 2007, 2009). We simulated spiking pyramidal interneuronal gamma (PING) whose period is regulated by the decay time constant of GABAA-mediated synaptic inhibition and also subthreshold gamma driven by gamma-periodic exogenous excitatory synaptic drive. Our model predicts distinguishable CD features created by spiking PING compared to subthreshold driven gamma that can help to disambiguate mechanisms of gamma oscillations in human signals. We found that gamma rhythms in neocortical layer 5 can obscure a simultaneous, independent gamma in layer 2/3. Further, we arrived at a novel interpretation of the origin of high gamma frequency rhythms (100-150 Hz), showing that they emerged from a specific temporal feature of CDs associated with single cycles of PING activity and did not reflect a separate rhythmic process. Last we show that the emergence of observable subthreshold gamma required highly coherent exogenous drive. Our results are the first to demonstrate features of gamma oscillations in human current source signals that distinguish cellular and circuit level mechanisms of these rhythms and may help to guide understanding of their functional role.
Frontiers in Human Neuroscience 12/2013; 7:869. DOI:10.3389/fnhum.2013.00869 · 3.63 Impact Factor
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