Astrocytes contribute to gamma oscillations and recognition memory

Abstract

Glial cells are an integral part of functional communication in the brain. Here we show that astrocytes contribute to the fast dynamics of neural circuits that underlie normal cognitive behaviors. In particular, we found that the selective expression of tetanus neurotoxin (TeNT) in astrocytes significantly reduced the duration of carbachol-induced gamma oscillations in hippocampal slices. These data prompted us to develop a novel transgenic mouse model, specifically with inducible tetanus toxin expression in astrocytes. In this in vivo model, we found evidence of a marked decrease in electroencephalographic (EEG) power in the gamma frequency range in awake-behaving mice, whereas neuronal synaptic activity remained intact. The reduction in cortical gamma oscillations was accompanied by impaired behavioral performance in the novel object recognition test, whereas other forms of memory, including working memory and fear conditioning, remained unchanged. These results support a key role for gamma oscillations in recognition memory. Both EEG alterations and behavioral deficits in novel object recognition were reversed by suppression of tetanus toxin expression. These data reveal an unexpected role for astrocytes as essential contributors to information processing and cognitive behavior.glia | electroencephalogram | network oscillation | gliotransmitter | glial fibrillary acidic protein I n the brain, the spatial and temporal coordination of networks of cells underlies both homeostatic and cognitive functions. Such synchronous activity gives rise to fluctuating local field potentials that can be recorded on the surface of the scalp by electroencephalography (EEG). Fast local field potential oscillations in the gamma frequency band (γ 25-80 Hz) have been closely correlated with learning, memory storage and retrieval, attention, and other cognitive or motor functions (1). In addition, in several neuropsychiatric disorders, gamma oscillations exhibit significant abnormalities that often correlate with the severity of the symptoms: a reduction in gamma oscillations is characteristic of the negative symptoms of schizophrenia, Alzheimer's disease, and autism, whereas the positive symptoms of schizophrenia, epilepsy, and attention-deficit hyperactivity disorder show increased gamma amplitudes (2). Nonetheless, the molecular mechanisms underlying these oscillations are poorly understood. Although the inhibitory interneurons (3, 4) and neuronal gap junction proteins 6) have all been shown to contribute to gamma oscillations, many of the molecular, cellular, and network mechanistic details underlying oscillations still remain undefined. Furthermore, the role of oscillations in brain function and behavior has yet to be fully clarified.In the present work, we have moved away from the traditional focus of network oscillation research, namely neurons, and have instead investigated the consequences of a functional manipulation of astrocytes on network function and animal behavior. The role of astrocytes in maintaining the brain's en...

Astrocytes regulate cortical state switching in vivo

“…Due to their syncytial architecture and slower Ca 2+ signaling, astrocytes may be gathering information from across many cells and synapses at longer timescales than neurons may be able to, to regulate this shift. Thus, it will be important to measure and manipulate astrocytes' activity in a range of vigilance states and behavioral/sensory tasks to fully understand their role in state shifts (27,28,29). The causal links between astrocyte activity and circuit function we uncover indicate that astrocytes are actively involved in neural circuits necessary for key brain functions such as sleep, memory, and sensory processing.…”

“…However, the methodology used to demonstrate an astrocyte-specific function in regulation of SWS (21) and the slow oscillation (22) has become controversial (25,26), leaving astrocytes' role in the generation of the slow-oscillation state uncertain. In addition, there are few data on astrocytes' roles in acute changes in brain state, as these previous in vivo studies of oscillations have used longer-term, transcription-based manipulations of astrocyte function (21,22,27). And although astrocytic activity may be acutely shaped by neuromodulatory signals similar to neurons during brain state changes (28,29), these effects do not specifically address the causal role that astrocytes may play in these shifts.…”

A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior

“…Reduction in cortical γ oscillations has been associated with defects of mouse behavior in the non-associative exploratory task of novel object recognition (NOR) (Lee et al., 2014). We thus probed memory abilities in Slm2 -null mice using this task, which consisted of exposing them to one previously presented object (Familiar Object, FO) together with an unfamiliar object (Novel Object, NO) (Figure 7B).…”

Dynamic Network Communication as a Unifying Neural Basis for Cognition, Development, Aging, and Disease

“…The fact that population spiking and the oscillatory frequency of a neuronal population can be different from the spiking frequency of individual neurons in the neural region generating the oscillation (72; 73), and that some oscillatory processes may have non-neuronal (glial) origins that affect behavior and neural communication (80; 81), suggests that spiking and oscillations are distinct. However, as noted above, oscillations and spiking interact with externally-applied electric fields to modulate network activity in humans (82), non-human primates (83), and rats (7).…”