Signalling from neurones to astrocytes

Stimulation of neurones or neuronal afferents triggers Ca2+ signalling in astrocytes both in cell cultures and in situ in brain slices. Moreover, astroglial cells are able to distinguish the intensity of neuronal activity. Astroglial Ca2+ oscillations induced by neuronal stimulation are clearly frequency encoded, the frequency increasing following an increase in synaptic activity. For example, it was found that astrocytes in hippocampus were able to follow the frequency of stimulation of neuronal afferents. The low frequency stimulation of neuronal fibres (the so-called Schaffer collaterals, through which neurones in the CA3 area are synaptically connected with neurones in the CA1 region) did not evoke any responses in astrocytes surrounding the synaptic terminals. High frequency stimulation, however, evoked repetitive Ca2+ signals in astrocytes, and the frequency of astroglial [Ca2+]j elevations was directly dependent on the frequency or intensity of stimulation -increases in either led to a more frequent astrocytic response. Importantly, the Ca2+ responses in astrocytic processes were asynchronous, indicating the existence of relatively isolated compartments, able to follow activation of single synapses or small groups of synapses surrounded by a particular process. Similar to neurones, astrocytes also display cellular memory: periods of intense synaptic stimulation induce a long-lasting potentiation of the frequency of the subsequent responses (Figure 6.4). This phenomenon indeed resembles the long-term potentiation (LTP) of synaptic activity in neurones, in which intense synaptic stimulation

Schwann Cell

Figure 6.4 Long-term plasticity of astroglial Ca2+ signals. Astroglial Ca2+ signals undergo a long-term plasticity following periods of intense stimulation of presynaptic inputs, in a manner similar to neuronal postsynaptic electrical responses. The scheme shows a central glutamatergic synapse. Electrical stimulation of the terminal triggers excitatory postsynaptic potentials (EPSPs) in the neurone and Ca2+ signals in glial processes surrounding the synapse. Intense stimulation of synaptic inputs results in a long-term increase in the amplitude of the EPSP in the postsynaptic neurone (the phenomenon known as long-term potentiation, LTP), and in astrocytes results in a long-term increase in the frequency of glial Ca2+ responses. (Modified from Carmignoto G (2000) Reciprocal communication systems between astrocytes and neurones. Prog Neurobiol 62, 561-581)

Figure 6.4 Long-term plasticity of astroglial Ca2+ signals. Astroglial Ca2+ signals undergo a long-term plasticity following periods of intense stimulation of presynaptic inputs, in a manner similar to neuronal postsynaptic electrical responses. The scheme shows a central glutamatergic synapse. Electrical stimulation of the terminal triggers excitatory postsynaptic potentials (EPSPs) in the neurone and Ca2+ signals in glial processes surrounding the synapse. Intense stimulation of synaptic inputs results in a long-term increase in the amplitude of the EPSP in the postsynaptic neurone (the phenomenon known as long-term potentiation, LTP), and in astrocytes results in a long-term increase in the frequency of glial Ca2+ responses. (Modified from Carmignoto G (2000) Reciprocal communication systems between astrocytes and neurones. Prog Neurobiol 62, 561-581)

induces a long-lasting increase in the amplitude of post-synaptic potentials. The only difference between neurones and glia is in the parameter under regulation: in neurones this is the amplitude of the response, whereas in astrocytes it is the frequency.

A similar organization of glial responses to activation of neuronal afferents was also observed in Bergmann glial cells in the cerebellum. Fine processes of Bergmann glia enwrap synaptic terminals formed by parallel fibres on dendrites of Purkinje neurones. Stimulation of these parallel fibres resulted in highly localized Ca2+ signals in the processes of Bergmann glial cells (Figure 6.5), once more indicating the existence of relatively independent signalling microdomains, which can be individually activated by release of neurotransmitter from closely associated synaptic terminals.

STIM

STIM

Bergmann Glial Cells

Figure 6.5 Localized intracellular Ca2+ signals in processes of Bergmann glial cells in response to synaptic activity:

A. Experimental protocol. Parallel fibres (PF) were stimulated via a pipette connected to a stimulator (STIM) while calcium-dependent fluorescence responses were recorded in a Bergmann glial cell (BG); PCL, Purkinje cell layer.

B. The left panel shows a confocal fluorescence intensity image of a patch-clamped Bergmann glial cell dialyzed with a calcium-sensitive dye (Oregon green 488 BAPTA-1). Three processes were distinguished (indicated as ®-®). Calcium signals in response to PF stimulation were measured independently in each process. The responding process (®) was subdivided into five regions of interest (marked 1-5), in which calcium signals were measured separately (middle panel; time of PF stimulation marked by an arrow and a dotted line).

C. Schematic representation of a Bergmann glial microdomain. The basic components of the microdomain, the stalk and the 'head', are shown together with their relationships to the neighbouring neuronal elements. Stimulation of several closely positioned parallel fibres may activate a single microdomain, inducing both membrane currents and local Ca2+ signals. (Modified from Grosche J, Matyash V, Moller T, Verkhratsky A, Reichenbach A, Kettenmann H (1999) Microdomains for neuron-glia interaction: parallel fiber signaling to Bergmann glial cells. Nat Neurosci 2,139-143; and from Grosche J, Kettenmann H, Reichenbach A (2002) Bergmann glial cells form distinct morphological structures to interact with cerebellar neurons. J Neurosci Res 68, 138-149)

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