Synaptic Plasticity in Cortical Inhibitory Neurons: What Mechanisms May Help to Balance Synaptic Weight Changes?

Front Cell Neurosci. 2020 Sep 4;14:204. doi: 10.3389/fncel.2020.00204. eCollection 2020.


Inhibitory neurons play a fundamental role in the normal operation of neuronal networks. Diverse types of inhibitory neurons serve vital functions in cortical networks, such as balancing excitation and taming excessive activity, organizing neuronal activity in spatial and temporal patterns, and shaping response selectivity. Serving these, and a multitude of other functions effectively requires fine-tuning of inhibition, mediated by synaptic plasticity. Plasticity of inhibitory systems can be mediated by changes at inhibitory synapses and/or by changes at excitatory synapses at inhibitory neurons. In this review, we consider that latter locus: plasticity at excitatory synapses to inhibitory neurons. Despite the fact that plasticity of excitatory synaptic transmission to interneurons has been studied in much less detail than in pyramids and other excitatory cells, an abundance of forms and mechanisms of plasticity have been observed in interneurons. Specific requirements and rules for induction, while exhibiting a broad diversity, could correlate with distinct sources of excitatory inputs and distinct types of inhibitory neurons. One common requirement for the induction of plasticity is the rise of intracellular calcium, which could be mediated by a variety of ligand-gated, voltage-dependent, and intrinsic mechanisms. The majority of the investigated forms of plasticity can be classified as Hebbian-type associative plasticity. Hebbian-type learning rules mediate adaptive changes of synaptic transmission. However, these rules also introduce intrinsic positive feedback on synaptic weight changes, making plastic synapses and learning networks prone to runaway dynamics. Because real inhibitory neurons do not express runaway dynamics, additional plasticity mechanisms that counteract imbalances introduced by Hebbian-type rules must exist. We argue that weight-dependent heterosynaptic plasticity has a number of characteristics that make it an ideal candidate mechanism to achieve homeostatic regulation of synaptic weight changes at excitatory synapses to inhibitory neurons.

Keywords: heterosynaptic plasticity; hippocampus; homeostasis; homosynaptic plasticity; inhibitory neurons; neocortex; synaptic plasticity.

Publication types

  • Review