Corticothalamic Projections Gate Alpha Rhythms in the Pulvinar

Two types of corticothalamic (CT) terminals reach the pulvinar nucleus of the thalamus, and their distribution varies according to the hierarchical level of the cortical area they originate from. While type 2 terminals are more abundant at lower hierarchical levels, terminals from higher cortical areas mostly exhibit type 1 axons. Such terminals also evoke different excitatory postsynaptic potential dynamic profiles, presenting facilitation for type 1 and depression for type 2. As the pulvinar is involved in the oscillatory regulation between intercortical areas, fundamental questions about the role of these different terminal types in the neuronal communication throughout the cortical hierarchy are yielded. Our theoretical results support that the co-action of the two types of terminals produces different oscillatory rhythms in pulvinar neurons. More precisely, terminal types 1 and 2 produce alpha-band oscillations at a specific range of connectivity weights. Such oscillatory activity is generated by an unstable transition of the balanced state network’s properties that it is found between the quiescent state and the stable asynchronous spike response state. While CT projections from areas 17 and 21a are arranged in the model as the empirical proportion of terminal types 1 and 2, the actions of these two cortical connections are antagonistic. As area 17 generates low-band oscillatory activity, cortical area 21a shifts pulvinar responses to stable asynchronous spiking activity and vice versa when area 17 produces an asynchronous state. To further investigate such oscillatory effects through corticothalamo-cortical projections, the transthalamic pathway, we created a cortical feedforward network of two cortical areas, 17 and 21a, with CT connections to a pulvinar-like network with two cortico-recipient compartments. With this model, the transthalamic pathway propagates alpha waves from the pulvinar to area 21a. This oscillatory transfer ceases when reciprocal connections from area 21a reach the pulvinar, closing the CT loop. Taken together, results of our model suggest that the pulvinar shows a bi-stable spiking activity, oscillatory or regular asynchronous spiking, whose responses are gated by the different activation of cortico-pulvinar projections from lower to higher-order areas such as areas 17 and 21a.

Corticothalamic Projections Gate Alpha Rhythms in the Pulvinar

Two types of corticothalamic (CT) terminals reach the pulvinar nucleus of the thalamus, and their distribution varies according to the hierarchical level of the cortical area they originate from. While type 2 terminals are more abundant at lower hierarchical levels, terminals from higher cortical areas mostly exhibit type 1 axons. Such terminals also evoke different excitatory postsynaptic potential dynamic profiles, presenting facilitation for type 1 and depression for type 2. As the pulvinar is involved in the oscillatory regulation between intercortical areas, fundamental questions about the role of these different terminal types in the neuronal communication throughout the cortical hierarchy are yielded. Our theoretical results support that the co-action of the two types of terminals produces different oscillatory rhythms in pulvinar neurons. More precisely, terminal types 1 and 2 produce alpha-band oscillations at a specific range of connectivity weights. Such oscillatory activity is generated by an unstable transition of the balanced state network’s properties that it is found between the quiescent state and the stable asynchronous spike response state. While CT projections from areas 17 and 21a are arranged in the model as the empirical proportion of terminals types 1 and 2, the actions of these two cortical connections are antagonistic. As area 17 generates low-band oscillatory activity, cortical area 21a shifts pulvinar responses to stable asynchronous spiking activity and vice-versa when area 17 produces an asynchronous state. To further investigate such oscillatory effects through corticothalamo-cortical projections, the transthalamic pathway, we created a cortical feedforward network of two cortical areas, 17 and 21a, with CT connections to a pulvinar-like network. With this model, the transthalamic pathway propagates alpha waves from the pulvinar to area 21a. This oscillatory transfer ceases when reciprocal connections from area 21a reach the pulvinar, closing the cortico-thalamic loop. Taken together, results of our model suggest that the pulvnar shows a bi-stable spiking activity, oscillatory or regular asynchronous spiking, whose responses are gated by the different activation of cortico-pulvinar projections from lower to higher-order areas such as areas 17 and 21a.

Characterization of Feedback Neurons in the High-Level Visual Cortical Areas That Project Directly to the Primary Visual Cortex in the Cat

Previous studies indicate that top-down influence plays a critical role in visual information processing and perceptual detection. However, the substrate that carries top-down influence remains poorly understood. Using a combined technique of retrograde neuronal tracing and immunofluorescent double labeling, we characterized the distribution and cell type of feedback neurons in cat’s high-level visual cortical areas that send direct connections to the primary visual cortex (V1: area 17). Our results showed: (1) the high-level visual cortex of area 21a at the ventral stream and PMLS area at the dorsal stream have a similar proportion of feedback neurons back projecting to the V1 area, (2) the distribution of feedback neurons in the higher-order visual area 21a and PMLS was significantly denser than in the intermediate visual cortex of area 19 and 18, (3) feedback neurons in all observed high-level visual cortex were found in layer II–III, IV, V, and VI, with a higher proportion in layer II–III, V, and VI than in layer IV, and (4) most feedback neurons were CaMKII-positive excitatory neurons, and few of them were identified as inhibitory GABAergic neurons. These results may argue against the segregation of ventral and dorsal streams during visual information processing, and support “reverse hierarchy theory” or interactive model proposing that recurrent connections between V1 and higher-order visual areas constitute the functional circuits that mediate visual perception. Also, the corticocortical feedback neurons from high-level visual cortical areas to the V1 area are mostly excitatory in nature.

Pulvinar Modulates Synchrony across Visual Cortical Areas

The cortical visual hierarchy communicates in different oscillatory ranges. While gamma waves influence the feedforward processing, alpha oscillations travel in the feedback direction. Little is known how this oscillatory cortical communication depends on an alternative route that involves the pulvinar nucleus of the thalamus. We investigated whether the oscillatory coupling between the primary visual cortex (area 17) and area 21a depends on the transthalamic pathway involving the pulvinar in cats. To that end, visual evoked responses were recorded in areas 17 and 21a before, during and after inactivation of the pulvinar. Local field potentials were analyzed with Wavelet and Granger causality tools to determine the oscillatory coupling between layers. The results indicate that cortical oscillatory activity was enhanced during pulvinar inactivation, in particular for area 21a. In area 17, alpha band responses were represented in layers II/III. In area 21a, gamma oscillations, except for layer I, were significantly increased, especially in layer IV. Granger causality showed that the pulvinar modulated the oscillatory information between areas 17 and 21a in gamma and alpha bands for the feedforward and feedback processing, respectively. Together, these findings indicate that the pulvinar is involved in the mechanisms underlying oscillatory communication along the visual cortex.

Hierarchical Organization of Corticothalamic Projections to the Pulvinar

Signals from lower cortical visual areas travel to higher-order areas for further processing through cortico-cortical projections, organized in a hierarchical manner. These signals can also be transferred between cortical areas via alternative cortical transthalamic routes involving higher-order thalamic nuclei like the pulvinar. It is unknown whether the organization of transthalamic pathways may reflect the cortical hierarchy. Two axon terminal types have been identified in corticothalamic (CT) pathways: the types I (modulators) and II (drivers) characterized by thin axons with small terminals and by thick axons and large terminals, respectively. In cats, projections from V1 to the pulvinar complex comprise mainly type II terminals, whereas those from extrastriate areas include a combination of both terminals suggesting that the nature of CT terminals varies with the hierarchical order of visual areas. To test this hypothesis, distribution of CT terminals from area 21a was charted and compared with 3 other visual areas located at different hierarchical levels. Results demonstrate that the proportion of modulatory CT inputs increases along the hierarchical level of cortical areas. This organization of transthalamic pathways reflecting cortical hierarchy provides new and fundamental insights for the establishment of more accurate models of cortical signal processing along transthalamic cortical pathways.

Pulvinar Modulates Contrast Responses in the Visual Cortex as a Function of Cortical Hierarchy

The pulvinar is the largest extrageniculate visual nucleus in mammals. Given its extensive reciprocal connectivity with the visual cortex, it allows the cortico-thalamocortical transfer of visual information. Nonetheless, knowledge of the nature of the pulvinar inputs to the cortex remains elusive. We investigated the impact of silencing the pulvinar on the contrast response function of neurons in 2 distinct hierarchical cortical areas in the cat (areas 17 and 21a). Pulvinar inactivation altered the response gain in both areas, but with larger changes observed in area 21a. A theoretical model was proposed, simulating the pulvinar contribution to cortical contrast responses by modifying the excitation-inhibition balanced state of neurons across the cortical hierarchy. Our experimental and theoretical data showed that the pulvinar exerts a greater modulatory influence on neuronal activity in area 21a than in the primary visual cortex, indicating that the pulvinar impact on cortical visual neurons varies along the cortical hierarchy.

Gamma-rhythmic Gain Modulation

SummaryCognition requires the dynamic modulation of effective connectivity, i.e. the modulation of the postsynaptic neuronal response to a given input. If postsynaptic neurons are rhythmically active, this might entail rhythmic gain modulation, such that inputs synchronized to phases of high gain benefit from enhanced effective connectivity. We show that visually induced gamma-band activity in awake macaque area V4 rhythmically modulates responses to unpredictable stimulus events. This modulation exceeded a simple additive superposition of a constant response onto ongoing gamma-rhythmic firing, demonstrating the modulation of multiplicative gain. Gamma phases leading to strongest neuronal responses also led to shortest behavioral reaction times, suggesting functional relevance of the effect. Furthermore, we find that constant optogenetic stimulation of anesthetized cat area 21a produces gamma-band activity entailing a similar gain modulation. As the gamma rhythm in area 21a did not spread backwards to area 17, this suggests that postsynaptic gamma is sufficient for gain modulation.