Astrocytes and Attention to the New

One of the many simplifying assumptions proposed for the brain simulations being attempted by just-starting, very large research programs in Europe and North America is that neural networks can be simulated as networks of neurons alone, abstracting away the influences of supporting cells such as oligodendrocytes and astrocytes, which account for a large portion of normal brain. Astrocytes, for example, make up about 50% of brain cellular mass.

Why might we assume that supporting glial cells like astrocytes can be ignored in simulation brain function, including components of cognition? The feeling has been that such cells are needed for the network of neurons to function at all, but that they did not determine particular aspects of cognition and so their influence could be safely averaged out of the network.

Unfortunately, there is increasing evidence that ignoring, or averaging out, the influence of astrocytes in simulating cognition may not be possible if we want to properly simulate some aspects of attention and memory, at least in mice. The article below, from PNAS this month, documents an influence of astrocytes on the gamma oscillation-dependent behavioral response to novelty in mice.

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ABSTRACT

Astrocytes contribute to gamma oscillations and recognition memory

Hosuk Sean Leea,b,1, Andrea Ghettia,2, António Pinto-Duartec,d,e, Xin Wangc, Gustavo Dziewczapolskia, Francesco Galimif,g, Salvador Huitron-Resendizh, Juan C. Piña-Crespoa,3, Amanda J. Robertsh, Inder M. Vermaf, Terrence J. Sejnowskic,i, and Stephen F. Heinemanna,1

Significance

Astrocytes are well placed to modulate neural activity. However, the functions typically attributed to astrocytes are associated with a temporal dimension significantly slower than the timescale of synaptic transmission of neurons. Consequently, it has been assumed that astrocytes do not play a major role in modulating fast neural network dynamics known to underlie cognitive behavior. By creating a transgenic mouse in which vesicular release from astrocytes can be reversibly blocked, we found that astrocytes are necessary for novel object recognition behavior and to maintain functional gamma oscillations both in vitro and in awake-behaving animals. Our findings reveal an unexpected role for astrocytes in neural information processing and cognition.

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.

Hosuk Sean Lee, doi: 10.1073/pnas.1410893111