Spontaneous Local Gamma Oscillation Selectively Enhances Neural Network Responsiveness

Synchronized oscillation is very commonly observed in many neuronal systems and might play an important role in the response properties of the system. We have studied how the spontaneous oscillatory activity affects the responsiveness of a neuronal network, using a neural network model of the visual cortex built from Hodgkin-Huxley type excitatory (E-) and inhibitory (I-) neurons. When the isotropic local E-I and I-E synaptic connections were sufficiently strong, the network commonly generated gamma frequency oscillatory firing patterns in response to random feed-forward (FF) input spikes. This spontaneous oscillatory network activity injects a periodic local current that could amplify a weak synaptic input and enhance the network's responsiveness. When E-E connections were added, we found that the strength of oscillation can be modulated by varying the FF input strength without any changes in single neuron properties or interneuron connectivity. The response modulation is proportional to the oscillation strength, which leads to self-regulation such that the cortical network selectively amplifies various FF inputs according to its strength, without requiring any adaptation mechanism. We show that this selective cortical amplification is controlled by E-E cell interactions. We also found that this response amplification is spatially localized, which suggests that the responsiveness modulation may also be spatially selective. This suggests a generalized mechanism by which neural oscillatory activity can enhance the selectivity of a neural network to FF inputs

Localization of the oscillation activity effect in large cortical network (2 mm by 2 mm).

<p>(A) In the center region (G1), cortical gamma oscillation is activated by the higher FF input rate (40 spikes/s). Surrounding neurons are divided into groups (G2∼G11) by their distance from the center, and spontaneous oscillation is inactivated due to the lower FF input rate (10 spikes/s). The control group (G_∞) property was separately achieved by a uniformly low FF input rate (10 spikes/s) network, as an approximation of infinitely distant neurons. Responsiveness and response delay measurements show that the properties of surrounding neurons (G2∼G6) are continuously distributed between G1 to G_∞ (insets), and distant groups (G7∼G11) show almost the same property as G_∞. (B) For FF inputs weaker than the FF response threshold (<30 µS/cm²), responsiveness and response delay changes gradually with the distance from the G1 boundary. The G2 property is very similar to that of G1, while G11 properties are almost the same as G_∞ properties. For stronger inputs (>30 µS/cm²), surrounding regions are not much influenced by G1 oscillation. Most surrounding group properties are similar to those of G_∞, showing clear localization of oscillation effect. For all FF input strength, the influence of oscillation is certainly restricted within local area. (C) The gamma oscillation effect localization is determined by the range of single neuron synaptic connections. The E- and I- synaptic connections of each single neuron are varied from their initial value (100%, radius of 200 µm for E- cells, 100 µm for I- cells), to 50% (100 µm for E- cells, 50 µm for I- cells). The ratio of E- to I- connections range (2∶1) was kept the same in all cases. The area of surrounding regions affected by the oscillation in the center region shrinks, as the E- and I- synaptic connection range is reduced. For comparisons, cortical responsiveness is normalized to the value of the center region in each case.</p

Modification of oscillation strength by various FF input strengths.

<p>(A) Cross-correlograms of cortical spikes. (i), (ii) In the OA network, the relative strength of gamma oscillation changes according to the FF input strength. The oscillation is strongest when FF input strength is 35∼40 µS/cm², and gradually diminishes as input strength increases. (iii) The E-I firing pattern shows that cortical oscillation is significantly modulated by the E-E interaction, and two different peaks coexist (‘spike doublets’, * and **). For a stronger FF input (50 µS/cm²), the E-I firing pattern shows only the normal gamma phase feature (***). Cortical oscillation is almost disappears for very strong FF input (80 µS/cm²). (B) The responsiveness difference between the OA network and the FF network changes from positive (for weak FF inputsthresh) to negative (for moderate FF inputs>S_thresh), and becomes zero (for strong FF inputs). Its absolute value (or cortical response modulation) is almost proportional to the strength of the gamma oscillation at each input strength (except at the FF response threshold, ∼30 µS/cm², where the difference changes from positive to negative). Also the difference in response delay between the OA network and the FF network is proportional to the strength of the gamma oscillation, which is controlled by the FF input strength.</p

Various cortical activity states.

<p>Raster plot of cortical output spikes, instantaneous FF input and cortical output firing rate, and cross-correlogram of cortical output spikes. (A) (i), (ii) When cortical synaptic connections are turned off, there is no correlated cortical activity. The output firing rate directly follows the FF input rate pattern. (iii) The E-I firing phase shows no correlation. (B) (i), (ii) When cortical connections are turned on, both E- and I- network neurons show oscillation patterns for a wide range of FF input and cortical parameters. This spike raster plot shows grating-like patterns, and the output firing rate oscillates with the gamma band frequency. The cross-correlogram pattern also shows a clear oscillation pattern. (iii) In this case, the E- and I- cells fire with little phase difference. This E-I firing pattern is different from normal gamma oscillation in the E-I phase, indicating that the contribution of the E-E interaction is significant in this case (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000342#pcbi-1000342-g001" target="_blank">Figure 1E</a>). (C) (i), (ii) The oscillation-inactive state can be achieved simply by lowering the FF input rate. The E-E cross-correlogram shows hardly any oscillation pattern, even though cortical connectivity is kept the same as in (B) and I- cells show oscillation patterns. The FF Input rate was 40 spikes/s for (A) and (B), and 10 spikes/s for (C). (iii) The E-I firing phase shows no clear correlation as in (A) (iii).</p

The E-I firing phase modulation by E-E coupling.

<p>Raster plot of E- and I- cells spikes (A) and spike trains in sample E- and I- cells (B). Only excitatory connections (E-E and E-I) are turned on, while inhibitory connections (I-E and I-I) are turned off. (A) At first, a small number of E- cells fire by FF input (i). These E- spikes stimulate nearby E- and I- cells by E-E and E-I connections respectively. Since the E-I connection is stronger than the E-E connection in this model, I- cells fire (ii) before E- cells fire (iii) in this cortical drive. The E- cells firing by means of the E-E interactions continues for a while, due to the self-feedback in the E-E interaction loop. As a result of this ‘lagged’ synchronization, the oscillation frequency is reduced. This duration of excitation causes the second firing of I- cells (iv) to make a ‘spike doublet’. The interval between the two spikes in a spike doublet is determined by the refractory period of I- cells. The first spike of a doublet forms the ‘E-E interaction modulated phase’ in the E-I firing phase, while the second spike forms the ‘normal’ gamma E-I phase. (B) I- cells occasionally produce ‘spike doublets’. The first I- spike in a doublet usually fires before nearby E- cells spike, while the second I- spike usually follows the E- spike. If inhibitory connections (I-E and I-I) are turned on, E- cells fire less than once in each cycle, and I- spike doublets appear less frequently.</p

Oscillation modulation without E-E interaction.

<p>(i) (ii) The cortical oscillation strength is weaker, and far less modified by the FF input, compared with <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000342#pcbi-1000342-g005" target="_blank">Figure 5A</a>. The oscillation pattern in E- cells disappears for both weak and strong FF inputs. (iii) The relative E-I firing phase does not change for weak inputs in this case, unlike that shown in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000342#pcbi-1000342-g005" target="_blank">Figure 5A</a> (iii).</p

Responsiveness and response delay of each cortical state.

<p>(A) The FF network has a step-like shape response function, with a threshold value of ∼30 µS/cm². The OA network shows a more gradual change in its response function with a plateau near the FF response threshold. Its responsiveness for weak FF inputs is much stronger than for the other two cases. The OI network shows little difference in its response function from that of the FF network. (B) The cortical response to a single FF input spike is fastest in the OA network for all input strengths. For weak FF inputs, the average response delay is much shorter in the OA network than in other network states. As the FF input strength increases, the difference between OA and OI networks becomes smaller. The FF network always shows the largest delay time, even for very strong FF inputs.</p

Responsiveness to weak FF inputs is enhanced by spontaneous cortical gamma frequency oscillation.

<p>(A) (i) Cortical connections are turned off (FF). Neurons receive only FF inputs. Each weak (<30 µS/cm²) FF input raises some current and voltage fluctuation but cannot cause a cortical output spike unless two or more inputs are closely paired (***). (ii) Cortical connections are turned on (OA). In the presence of cortical gamma oscillation, each neuron receives cortical spikes from nearby neurons. Since cortical activity has the gamma frequency oscillation pattern, each neuron is provided with a periodic current fluctuation. This cortical current amplifies weak FF inputs to drive output spikes (*). This response enhancement depends on the phase of oscillation, so a FF input at an oscillation node is not amplified (**). (B) The response probability of entire (paired+unpaired) and single (unpaired) FF inputs (weak input strength ∼25 µS/cm²) for different cortical activity states. In both cases (paired and unpaired), input spikes were chosen only if there were no other spikes within 20 ms before each input. Paired inputs have another input within 20 ms after each input. Cortical output spikes were counted as is their relative timing to each input spike were 0 ms). All three cases show a non-zero response peak for the entire input. For unpaired input, only the OA network can respond. In each correlogram, response probability was normalized by the number of proper (entire or unpaired) FF input spikes. For the responsiveness calculation (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000342#pcbi-1000342-g003" target="_blank">Figure 3A</a>), each peak area was measured above background activity level (dashed line). Background activities were measured within a window from −10 ms to 0 ms.</p