Lactate Attenuates Synaptic Transmission and Affects Brain Rhythms Featuring High Energy Expenditure.

Lactate shuttled from blood, astrocytes, and/or oligodendrocytes may serve as the major glucose alternative in brain energy metabolism. However, its effectiveness in fueling neuronal information processing underlying complex cortex functions like perception and memory is unclear. We show that sole lactate disturbs electrical gamma and theta-gamma oscillations in hippocampal networks by either attenuation or neural bursts.

Mild metabolic stress is sufficient to disturb the formation of pyramidal cell ensembles during gamma oscillations.

Disturbances of cognitive functions occur rapidly during acute metabolic stress. However, the underlying mechanisms are not fully understood. Cortical gamma oscillations (30-100 Hz) emerging from precise synaptic transmission between excitatory principal neurons and inhibitory interneurons, such as fast-spiking GABAergic basket cells, are associated with higher brain functions, like sensory perception, selective attention and memory formation.

The mitochondrial calcium uniporter is crucial for the generation of fast cortical network rhythms.

The role of the mitochondrial calcium uniporter (MCU) gene () in cellular energy homeostasis and generation of electrical brain rhythms is widely unknown. We investigated this issue in mice and rats using -knockout and -knockdown strategies in vivo and in situ and determined the effects of these genetic manipulations on hippocampal gamma oscillations (30-70 Hz) and sharp wave-ripples. These physiological network states require precise neurotransmission between pyramidal cells and inhibitory interneurons, support spike-timing and synaptic plasticity and are associated with perception, attention and memory.

Metabolic modulation of neuronal gamma-band oscillations.

Gamma oscillations (30-100 Hz) represent a physiological fast brain rhythm that occurs in many cortex areas in awake mammals, including humans. They associate with sensory perception, voluntary movement, and memory formation and require precise synaptic transmission between excitatory glutamatergic neurons and inhibitory GABAergic interneurons such as parvalbumin-positive basket cells. Notably, gamma oscillations are exquisitely sensitive to shortage in glucose and oxygen supply (metabolic stress), with devastating consequences for higher cognitive functions.

Local oxygen homeostasis during various neuronal network activity states in the mouse hippocampus.

Cortical information processing comprises various activity states emerging from timed synaptic excitation and inhibition. However, the underlying energy metabolism is widely unknown. We determined the cerebral metabolic rate of oxygen (CMRO) along a tissue depth of <0.

Energy and Potassium Ion Homeostasis during Gamma Oscillations.

Fast neuronal network oscillations in the gamma frequency band (30-100 Hz) occur in various cortex regions, require timed synaptic excitation and inhibition with glutamate and GABA, respectively, and are associated with higher brain functions such as sensory perception, attentional selection and memory formation. However, little is known about energy and ion homeostasis during the gamma oscillation. Recent studies addressed this topic in slices of the rodent hippocampus using cholinergic and glutamatergic receptor models of gamma oscillations (GAM).

Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.

Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR).

A reliable model for gamma oscillations in hippocampal tissue.

Gamma oscillations (30-100 Hz) reflect a fast brain rhythm that provides a fundamental mechanism of complex neuronal information processing in the hippocampus and in the neocortex in vivo. Gamma oscillations have been implicated in higher brain functions, such as sensory perception, motor activity, and memory formation. Experimental studies on synaptic transmission and bioenergetics underlying gamma oscillations have primarily used acute slices of the hippocampus.

Energy substrates that fuel fast neuronal network oscillations.

Fast neuronal network oscillations in the gamma-frequency band (30--100 Hz) provide a fundamental mechanism of complex neuronal information processing in the hippocampus and neocortex of mammals. Gamma oscillations have been implicated in higher brain functions such as sensory perception, motor activity, and memory formation. The oscillations emerge from precise synapse interactions between excitatory principal neurons such as pyramidal cells and inhibitory GABAergic interneurons, and they are associated with high energy expenditure.