Neuronal Excitatory State Is Linked to Stress Resilience

The aging human brain is a study in both the importance and limitations of human stress response factors. Individual neurons can maintain functionality for 80 or more years, testifying to the potency of their stress response pathways. However, failure of these pathways during aging drastically increases the risk of neurodegenerative diseases. The transcriptional repressor REST is induced in the brains of long-lived humans but is lost in neurodegenerative disease. Here, we explore one modality of REST’s protective effects: regulation of neuronal excitability. We show that excitatory capacity and stress response are inversely correlated in the human brain. We find that REST and its C. elegans orthologs repress neuronal excitation in response to stressful conditions. Further, exogenously suppressing neuronal excitation restores stress resistance to REST-deficient animals, while enhancing stress response in wildtype ones. Thus, regulation of neuronal activity is an important aspect of neuronal stress response and a potential therapeutic modality.

Entraining corticocortical plasticity changes oscillatory activity in action control and inhibition

SummaryOscillatory activity may reflect interactions between brain areas[1]. Here we tested whether inducing corticocortical plasticity in a specific set of connections changes oscillatory activity and cortico-cortical interactions and, if this is the case, whether the changes manifest in a manner that is behaviour state-dependent. We either increased or decreased the influence of activity in human ventral premotor cortex (PMv) over activity in primary motor cortex (M1) using cortico-cortical paired associative stimulation (ccPAS)[2, 3]. Before and after stimulation participants performed a Go/No-Go task. While M1 TMS pulses revealed the excitatory state of the motor system at specific time points, the electroencephalogram (EEG) revealed the evolution of oscillatory activity dynamics in the motor system over several hundreds of milliseconds before, during, and after each movement. Augmenting cortical connectivity between PMv and M1, by evoking synchronous pre- and postsynaptic activity in the PMv-M1 pathways, led to a state-dependent modulation of the causal influence of PMv over M1, and at the same time, enhanced oscillatory beta and theta rhythms in Go and No-Go trials, respectively. No changes were observed in the alpha rhythm. The plasticity induction effect was dependent on PMv-M1 stimulation order; the opposite patterns of results were observed after an equal amount of stimulation of PMv and M1 but applied in a temporal pattern that did not augment PMv’s influence over M1. These results are consistent with Hebbian principles of synaptic plasticity[4] and show that artificial manipulation of cortico-cortical connectivity produces state-dependent functional changes in the spectral fingerprints of the motor circuit.

Sub-second dynamics of theta-gamma coupling in hippocampal CA1

Oscillatory brain activity reflects different internal brain states including neurons’ excitatory state and synchrony among neurons. However, characterizing these states is complicated by the fact that different oscillations are often coupled, such as gamma oscillations nested in theta in the hippocampus, and changes in coupling are thought to reflect distinct states. Here, we describe a new method to separate single oscillatory cycles into distinct states based on frequency and phase coupling. Using this method, we identified four theta-gamma coupling states in rat hippocampal CA1. These states differed in abundance across behaviors, phase synchrony with other hippocampal subregions, and neural coding properties suggesting that these states are functionally distinct. We captured cycle-to-cycle changes in oscillatory coupling states and found frequent switching between theta-gamma states showing that the hippocampus rapidly shifts between different functional states. This method provides a new approach to investigate oscillatory brain dynamics broadly.