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Short-term ionic plasticity at GABAergic synapses.

Raimondo JV, Markram H, Akerman CJ - Front Synaptic Neurosci (2012)

Bottom Line: This involves short-lasting changes to the ionic driving force for the post-synaptic receptors, a process referred to as short-term ionic plasticity.These changes are directly related to the history of activity at inhibitory synapses and are influenced by a variety of factors including the location of the synapse and the post-synaptic cell's ion regulation mechanisms.We explore the processes underlying this form of plasticity, when and where it can occur, and how it is likely to impact network activity.

View Article: PubMed Central - PubMed

Affiliation: Akerman Lab, Department of Pharmacology, Oxford University Oxford, Oxfordshire, UK.

ABSTRACT
Fast synaptic inhibition in the brain is mediated by the pre-synaptic release of the neurotransmitter γ-Aminobutyric acid (GABA)and the post-synaptic activation of GABA-sensitive ionotropic receptors. As with excitatory synapses, it is being increasinly appreciated that a variety of plastic processes occur at inhibitory synapses, which operate over a range of timescales. Here we examine a form of activity-dependent plasticity that is somewhat unique to GABAergic transmission. This involves short-lasting changes to the ionic driving force for the post-synaptic receptors, a process referred to as short-term ionic plasticity. These changes are directly related to the history of activity at inhibitory synapses and are influenced by a variety of factors including the location of the synapse and the post-synaptic cell's ion regulation mechanisms. We explore the processes underlying this form of plasticity, when and where it can occur, and how it is likely to impact network activity.

No MeSH data available.


Related in: MedlinePlus

Intense GABAAR activation results in Cl− accumulation more readily in smaller volume compartments of the cell, than in larger volume compartments. A CA3 hippocampal pyramidal cell within a P14 hippocampal slice culture was patched using the gramicidin perforated patch technique. HCO−3 was excluded from the external solution to ensure that GABAAR currents were purely attributable to Cl−. GABAAR activation was evoked by local application of 100 μM GABA to either the dendrites (top) or soma (bottom) of the neuron. In voltage clamp mode, Cl− was loaded by stepping the membrane voltage to −37.5 mV during application of the first “loading” puff (“GABA load”), before returning to −60 mV for the second “test” puff (“GABA test”). When the puffer pipette was positioned over the dendrites, a Cl− load affected the size and direction of the GABAAR current observed in response to the “test” puff. In contrast, this effect was not seen when a similar Cl− load was generated at the soma.
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Figure 2: Intense GABAAR activation results in Cl− accumulation more readily in smaller volume compartments of the cell, than in larger volume compartments. A CA3 hippocampal pyramidal cell within a P14 hippocampal slice culture was patched using the gramicidin perforated patch technique. HCO−3 was excluded from the external solution to ensure that GABAAR currents were purely attributable to Cl−. GABAAR activation was evoked by local application of 100 μM GABA to either the dendrites (top) or soma (bottom) of the neuron. In voltage clamp mode, Cl− was loaded by stepping the membrane voltage to −37.5 mV during application of the first “loading” puff (“GABA load”), before returning to −60 mV for the second “test” puff (“GABA test”). When the puffer pipette was positioned over the dendrites, a Cl− load affected the size and direction of the GABAAR current observed in response to the “test” puff. In contrast, this effect was not seen when a similar Cl− load was generated at the soma.

Mentions: Computational models (Qian and Sejnowski, 1990; Staley and Proctor, 1999; Doyon et al., 2011; Jedlicka et al., 2011) predict that for a given amount of synaptic GABAAR activation and its accompanying Cl− influx, smaller post-synaptic volumes will result in relatively larger increases in [Cl−]i and hence greater depolarizing shifts in EGABA. This explains the experimental finding that depolarizing responses to GABAAR activation are more easily elicited over dendritic as opposed to somatic compartments (Figure 2 and Staley and Proctor, 1999). In a theoretical paper, Qian and Sejnowski (1990) employed this reasoning to suggest that GABAAR-mediated inhibition is likely to be ineffective on dendritic spines. Due to their minute volume, even small amounts of Cl− influx into a spine would be predicted to cause a local increase in [Cl−]i that would rapidly depolarize EGABA. Consistent with this idea, it has since been confirmed that most GABAergic synapses are localized to dendritic shafts as opposed to spines (Freund and Buzsáki, 1996; Megías et al., 2001). In a similar vein, distal dendrites, apical tufts and the axon are also predicted to be prone to Cl− accumulation effects (Doyon et al., 2011). In addition to their small volume, the narrow diameter of these processes means that longitudinal diffusion of Cl− to other parts of the cell is severely restricted. This implies that multiple dendrite-targeting GABAergic inputs originating from a single pre-synaptic cell would have a larger inhibitory effect if the synapses are distributed throughout the dendritic tree, as opposed to being clustered along a single branch. Once again, such a morphological arrangement appears to be evident in different systems (Doyon et al., 2011; Jedlicka et al., 2011).


Short-term ionic plasticity at GABAergic synapses.

Raimondo JV, Markram H, Akerman CJ - Front Synaptic Neurosci (2012)

Intense GABAAR activation results in Cl− accumulation more readily in smaller volume compartments of the cell, than in larger volume compartments. A CA3 hippocampal pyramidal cell within a P14 hippocampal slice culture was patched using the gramicidin perforated patch technique. HCO−3 was excluded from the external solution to ensure that GABAAR currents were purely attributable to Cl−. GABAAR activation was evoked by local application of 100 μM GABA to either the dendrites (top) or soma (bottom) of the neuron. In voltage clamp mode, Cl− was loaded by stepping the membrane voltage to −37.5 mV during application of the first “loading” puff (“GABA load”), before returning to −60 mV for the second “test” puff (“GABA test”). When the puffer pipette was positioned over the dendrites, a Cl− load affected the size and direction of the GABAAR current observed in response to the “test” puff. In contrast, this effect was not seen when a similar Cl− load was generated at the soma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472547&req=5

Figure 2: Intense GABAAR activation results in Cl− accumulation more readily in smaller volume compartments of the cell, than in larger volume compartments. A CA3 hippocampal pyramidal cell within a P14 hippocampal slice culture was patched using the gramicidin perforated patch technique. HCO−3 was excluded from the external solution to ensure that GABAAR currents were purely attributable to Cl−. GABAAR activation was evoked by local application of 100 μM GABA to either the dendrites (top) or soma (bottom) of the neuron. In voltage clamp mode, Cl− was loaded by stepping the membrane voltage to −37.5 mV during application of the first “loading” puff (“GABA load”), before returning to −60 mV for the second “test” puff (“GABA test”). When the puffer pipette was positioned over the dendrites, a Cl− load affected the size and direction of the GABAAR current observed in response to the “test” puff. In contrast, this effect was not seen when a similar Cl− load was generated at the soma.
Mentions: Computational models (Qian and Sejnowski, 1990; Staley and Proctor, 1999; Doyon et al., 2011; Jedlicka et al., 2011) predict that for a given amount of synaptic GABAAR activation and its accompanying Cl− influx, smaller post-synaptic volumes will result in relatively larger increases in [Cl−]i and hence greater depolarizing shifts in EGABA. This explains the experimental finding that depolarizing responses to GABAAR activation are more easily elicited over dendritic as opposed to somatic compartments (Figure 2 and Staley and Proctor, 1999). In a theoretical paper, Qian and Sejnowski (1990) employed this reasoning to suggest that GABAAR-mediated inhibition is likely to be ineffective on dendritic spines. Due to their minute volume, even small amounts of Cl− influx into a spine would be predicted to cause a local increase in [Cl−]i that would rapidly depolarize EGABA. Consistent with this idea, it has since been confirmed that most GABAergic synapses are localized to dendritic shafts as opposed to spines (Freund and Buzsáki, 1996; Megías et al., 2001). In a similar vein, distal dendrites, apical tufts and the axon are also predicted to be prone to Cl− accumulation effects (Doyon et al., 2011). In addition to their small volume, the narrow diameter of these processes means that longitudinal diffusion of Cl− to other parts of the cell is severely restricted. This implies that multiple dendrite-targeting GABAergic inputs originating from a single pre-synaptic cell would have a larger inhibitory effect if the synapses are distributed throughout the dendritic tree, as opposed to being clustered along a single branch. Once again, such a morphological arrangement appears to be evident in different systems (Doyon et al., 2011; Jedlicka et al., 2011).

Bottom Line: This involves short-lasting changes to the ionic driving force for the post-synaptic receptors, a process referred to as short-term ionic plasticity.These changes are directly related to the history of activity at inhibitory synapses and are influenced by a variety of factors including the location of the synapse and the post-synaptic cell's ion regulation mechanisms.We explore the processes underlying this form of plasticity, when and where it can occur, and how it is likely to impact network activity.

View Article: PubMed Central - PubMed

Affiliation: Akerman Lab, Department of Pharmacology, Oxford University Oxford, Oxfordshire, UK.

ABSTRACT
Fast synaptic inhibition in the brain is mediated by the pre-synaptic release of the neurotransmitter γ-Aminobutyric acid (GABA)and the post-synaptic activation of GABA-sensitive ionotropic receptors. As with excitatory synapses, it is being increasinly appreciated that a variety of plastic processes occur at inhibitory synapses, which operate over a range of timescales. Here we examine a form of activity-dependent plasticity that is somewhat unique to GABAergic transmission. This involves short-lasting changes to the ionic driving force for the post-synaptic receptors, a process referred to as short-term ionic plasticity. These changes are directly related to the history of activity at inhibitory synapses and are influenced by a variety of factors including the location of the synapse and the post-synaptic cell's ion regulation mechanisms. We explore the processes underlying this form of plasticity, when and where it can occur, and how it is likely to impact network activity.

No MeSH data available.


Related in: MedlinePlus