| Summary: | The discovery of direct communication between astrocytes and neurons has
changed the perception of astrocytes from passive support cells to active partners in
information processing. Astrocytes express myriad neurotransmitter receptors and have
been shown to release neurotransmitters, allowing these cells to respond and signal to
adjacent neurons, respectively. Astrocytes can rapidly respond to neurotransmitters with a
rise in [Ca²⁺]i and astrocyte neurotransmitter release has been shown to be calcium
dependent. The purpose of this research was to investigate unknown aspects of astrocyteneuron
communication with in situ calcium imaging to improve our understanding of
how these cells interact functionally.
The first objective of this research was to determine whether extracellular
dopamine elicits astrocyte calcium transients in the prefrontal cortex (PFC). Astrocytes
from this area express dopamine receptors and dopamine is an important neurotransmitter
in the PFC. We found that astrocytes in PFC brain slices reliably respond to a high
concentration of dopamine ([50μM]) with [Ca²⁺]i transients, however these responses
were due to the activation of adrenoreceptors, not dopamine receptors. The inability of a
lower concentration of dopamine ([10μM]) to elicit astrocyte [Ca²⁺]i transients questions
the whether these cells can rapidly respond to PFC dopamine at physiological levels.
The second objective of this research was to investigate the extent that calcium
dependent glutamate release from astrocytes is able to influence neural activity. The best
studied mechanism of astrocyte gliotransmitter release is the calcium dependent release
of glutamate which has been demonstrated in single astrocytes in situ. We used the vasoactive peptide endothelin to preferentially elicit widespread astrocyte [Ca²⁺]i
transients astrocytes from hippocampal brain slices to determine whether the widespread
calcium rise in astrocytes was associated with a change in glutamate sensitive synaptic
transmission. Despite eliciting nearly ubiquitous astrocyte calcium responses, we
observed no change in glutamate sensitive synaptic transmission as measured by
extracellular field recordings. These results question the ability of astrocytes to acutely
influence synaptic transmission of a brain region.
Our findings do not support an acute role of calcium dependent communication
between astrocytes and neurons in rapid information processing in the systems we
investigated. === Medicine, Faculty of === Graduate
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