Emergence and fragmentation of the alpha-band driven by neuronal network dynamics

Rhythmic neuronal network activity underlies brain oscillations. To investigate how connected neuronal networks contribute to the emergence of the α-band and to the regulation of Up and Down states, we study a model based on synaptic short-term depression-facilitation with afterhyperpolarization (AHP). We found that the α-band is generated by the network behavior near the attractor of the Up-state. Coupling inhibitory and excitatory networks by reciprocal connections leads to the emergence of a stable α-band during the Up states, as reflected in the spectrogram. To better characterize the emergence and stability of thalamocortical oscillations containing α and δ rhythms during anesthesia, we model the interaction of two excitatory networks with one inhibitory network, showing that this minimal topology underlies the generation of a persistent α-band in the neuronal voltage characterized by dominant Up over Down states. Finally, we show that the emergence of the α-band appears when external inputs are suppressed, while fragmentation occurs at small synaptic noise or with increasing inhibitory inputs. To conclude, α-oscillations could result from the synaptic dynamics of interacting excitatory neuronal networks with and without AHP, a principle that could apply to other rhythms.

Nonlinearities between inhibition and T-type calcium channel activity bidirectionally regulate thalamic oscillations

Absence seizures result from 3 to 5 Hz generalized thalamocortical oscillations that depend on highly regulated inhibitory neurotransmission in the thalamus. Efficient reuptake of the inhibitory neurotransmitter GABA is essential, and reuptake failure worsens human seizures. Here, we show that blocking GABA transporters (GATs) in acute rat brain slices containing key parts of the thalamocortical seizure network modulates epileptiform activity. As expected, we found that blocking either GAT1 or GAT3 prolonged oscillations. However, blocking both GATs unexpectedly suppressed oscillations. Integrating experimental observations into single-neuron and network-level computational models shows how a non-linear dependence of T-type calcium channel gating on GABAB receptor activity regulates network oscillations. Receptor activity that is either too brief or too protracted fails to sufficiently open T-type channels necessary for sustaining oscillations. Only within a narrow range does prolonging GABAB receptor activity promote channel opening and intensify oscillations. These results have implications for therapeutics that modulate inhibition kinetics.

Nonlinearities between inhibition and T-type calcium channel activity bidirectionally regulate thalamic network oscillations

Absence seizures result from 3-5 Hz generalized thalamocortical oscillations that depend on highly regulated inhibitory neurotransmission in the thalamus. Efficient reuptake of the inhibitory neurotransmitter GABA is essential, and reuptake failure worsens seizures. Here, we show that blocking GABA transporters (GATs) in acute brain slices containing key parts of the thalamocortical seizure network modulates epileptiform activity. As expected, we found that blocking either GAT1 or GAT3 prolonged oscillations. However, blocking both GATs unexpectedly suppressed oscillations. Integrating experimental observations into single-neuron and network-level computational models shows how a non-linear dependence of T-type calcium channel opening on GABAB receptor activity regulates network oscillations. Receptor activity that is either too brief or too protracted fails to sufficiently open T-type channels necessary for sustaining oscillations. Only within a narrow range does prolonging GABAB receptor activity promote channel opening and intensify oscillations. These results have implications for therapeutics that modulate GABA transporters.

Aberrant thalamocortical coherence in an animal model of tinnitus

Electrophysiological and imaging studies from humans suggest that the phantom sound of tinnitus is associated with abnormal thalamocortical neural oscillations (dysrhythmia) and enhanced gamma band activity in the auditory cortex. However, these models have seldom been tested in animal models where it is possible to simultaneously assess the neural oscillatory activity within and between the thalamus and auditory cortex. To explore this issue, we used multichannel electrodes to examine the oscillatory behavior of local field potentials recorded in the rat medial geniculate body (MBG) and primary auditory cortex (A1) before and after administering a dose of sodium salicylate (SS) that reliably induces tinnitus. In the MGB, SS reduced theta, alpha, and beta oscillations and decreased coherence (synchrony) between electrode pairs in theta, alpha, and beta bands but increased coherence in the gamma band. Within A1, SS significantly increased gamma oscillations, decreased theta power, and decreased coherence between electrode pairs in theta and alpha bands but increased coherence in the gamma band. When coherence was measured between one electrode in the MGB and another in A1, SS decreased coherence in beta, alpha, and theta bands but increased coherence in the gamma band. SS also increased cross-frequency coupling between the phase of theta oscillations in the MGB and amplitude of gamma oscillations in A1. Altogether, our results suggest that SS treatment fundamentally alters the manner in which thalamocortical circuits communicate, leading to excessive cortical gamma power and synchronization, neurophysiological changes implicated in tinnitus. Our data provide support for elements of both the thalamocortical dysrhythmia (TD) and synchronization by loss of inhibition (SLIM) models of tinnitus, demonstrating that increased cortical gamma band activity is associated with both enhanced theta-gamma coupling as well as decreases alpha power/coherence between the MGB and A1. NEW & NOTEWORTHY There are no effective drugs to alleviate the phantom sound of tinnitus because the physiological mechanisms leading to its generation are poorly understood. Neural models of tinnitus suggest that it arises from abnormal thalamocortical oscillations, but these models have not been extensively tested. This article identifies abnormal thalamocortical oscillations in a drug-induced tinnitus model. Our findings open up new avenues of research to investigate whether cellular mechanisms underlying thalamocortical oscillations are causally linked to tinnitus.

Thalamocortical Networks

The thalamus and cerebral cortex are intimately linked through strong topographical connections, not only from the thalamus to the cortex, but also from the cortex back to the thalamus. As in many parts of the brain, the basic circuit of thalamocortical connectivity is relatively simple, although intracortical and corticocortical connectivity provides a high level of complexity. One of the basic operations of the thalamocortical network is the generation of rhythmic oscillations, which are now relatively well understood. In the normal brain, these thalamocortical oscillations typically occur during sleep, although their pathological counterparts may appear as seizures during sleep or waking. Unfortunately, the normal function of reciprocal thalamocortical connectivity during the waking state is still unknown. Even so, focused research is yielding insights into the properties of each of the cellular and synaptic components of these networks and how they interact to perform circuitwide operations.

Cortically coordinated NREM thalamocortical oscillations play an essential, instructive role in visual system plasticity

Two long-standing questions in neuroscience are how sleep promotes brain plasticity and why some forms of plasticity occur preferentially during sleep vs. wake. Establishing causal relationships between specific features of sleep (e.g., network oscillations) and sleep-dependent plasticity has been difficult. Here we demonstrate that presentation of a novel visual stimulus (a single oriented grating) causes immediate, instructive changes in the firing of mouse lateral geniculate nucleus (LGN) neurons, leading to increased firing-rate responses to the presented stimulus orientation (relative to other orientations). However, stimulus presentation alone does not affect primary visual cortex (V1) neurons, which show response changes only after a period of subsequent sleep. During poststimulus nonrapid eye movement (NREM) sleep, LGN neuron overall spike-field coherence (SFC) with V1 delta (0.5–4 Hz) and spindle (7–15 Hz) oscillations increased, with neurons most responsive to the presented stimulus showing greater SFC. To test whether coherent communication between LGN and V1 was essential for cortical plasticity, we first tested the role of layer 6 corticothalamic (CT) V1 neurons in coherent firing within the LGN-V1 network. We found that rhythmic optogenetic activation of CT V1 neurons dramatically induced coherent firing in LGN neurons and, to a lesser extent, in V1 neurons in the other cortical layers. Optogenetic interference with CT feedback to LGN during poststimulus NREM sleep (but not REM or wake) disrupts coherence between LGN and V1 and also blocks sleep-dependent response changes in V1. We conclude that NREM oscillations relay information regarding prior sensory experience between the thalamus and cortex to promote cortical plasticity.

Source-Space Cross-Frequency Amplitude-Amplitude Coupling in Tinnitus

The thalamocortical dysrhythmia (TCD) model has been influential in the development of theoretical explanations for the neurological mechanisms of tinnitus. It asserts that thalamocortical oscillations lock a region in the auditory cortex into an ectopic slow-wave theta rhythm (4–8 Hz). The cortical area surrounding this region is hypothesized to generate abnormal gamma (>30 Hz) oscillations (“edge effect”) giving rise to the tinnitus percept. Consequently, the model predicts enhanced cross-frequency coherence in a broad range between theta and gamma. In this magnetoencephalography study involving tinnitus and control cohorts, we investigated this prediction. Using beamforming, cross-frequency amplitude-amplitude coupling (AAC) was computed within the auditory cortices for frequencies (f1,f2) between 2 and 80 Hz. We find the AAC signal to decompose into two distinct components at low (f1,f2<30 Hz) and high (f1,f2>30 Hz) frequencies, respectively. Studying the correlation of AAC with several key covariates (age, hearing level (HL), tinnitus handicap and duration, and HL at tinnitus frequency), we observe a statistically significant association between age and low-frequency AAC. Contrary to the TCD predictions, however, we do not find any indication of statistical differences in AAC between tinnitus and controls and thus no evidence for the predicted enhancement of cross-frequency coupling in tinnitus.