Inhibitory and Excitatory Spike-Timing-Dependent Plasticity in the Auditory Cortex

Abstract

Summary Synapses are plastic and can be modified by changes of spike timing. While most studies of long-term synaptic plasticity focus on excitation, inhibitory plasticity may be critical for controlling information processing, memory storage, and overall excitability in neural circuits. Here we examine spike-timing-dependent plasticity (STDP) of inhibitory synapses onto layer 5 neurons in slices of mouse auditory cortex, together with concomitant STDP of excitatory synapses. Pairing pre- and postsynaptic spikes potentiated inhibitory inputs irrespective of precise temporal order within ~10 msec. This was in contrast to excitatory inputs, which displayed an asymmetrical STDP time window. These combined synaptic modifications both required NMDA receptor activation, and adjusted the excitatory-inhibitory ratio of events paired together with postsynaptic spiking. Finally, subthreshold events became suprathreshold, and the time window between excitation and inhibition became more precise. These findings demonstrate that cortical inhibitory plasticity requires interactions with co-activated excitatory synapses to properly regulate excitatory-inhibitory balance.

Bimodal stimulus timing-dependent plasticity in primary auditory cortex is altered after noise exposure with and without tinnitus

“…While one STDP learning rule does not "fit all" excitatory synaptic connections, variability in responses in most cases can be explained by differences in levels of postsynaptic depolarization and subsequent Ca 2ϩ influx during the pairing protocol (Zilberter et al 2009). This concept is supported by data showing that the balance between excitatory and inhibitory synapses dictates neural STDP in A1 in vitro (D'amour and Froemke 2015). When the excitatory to inhibitory synaptic ratio is higher, more Ca 2ϩ channel and NMDA receptor activation occurs during spike pairing due to the increased level of depolarization.…”

Inhibitory engrams in perception and memory

“…Similarly, at a theoretical level, the precise learning rule responsible for inhibitory potentiation remains open to debate (25) because the implementation of alternative learning rules can also successfully account for cortical rebalancing (26). Nevertheless, additional empirical investigations in rodent auditory cortex emphasize the importance of inhibitory potentiation as a means to rebalance neural circuits, and show that nearcoincident pre-and postsynaptic activity is required (9). Furthermore, inhibitory potentiation is reported to be dependent upon NMDA receptors, suggesting that NMDA receptors act as coincidence detectors to coordinate plasticity between coactive excitatory and inhibitory neurons (27)(28)(29)(30).…”

“…A potentially important homeostatic mechanism is potentiation of inhibitory synapses, which occurs under specific conditions and acts to prevent excessive levels of postsynaptic activity (5)(6)(7)(8)(9)). An underappreciated property of this balancing process is that it naturally creates inhibitory representations or negative images of new, unbalanced excitatory patterns that arise within neural networks in response to experience (10,11).…”

Neural oligarchy: how synaptic plasticity breeds neurons with extreme influence

“…Their model relies 525 on a hypothesized metaplasticity mechanism, for which experimental evidence seems to 526 be lacking so far. In contrast, our model is capable of producing these distributions with 527 only well-established plasticity mechanisms [15,26,28,43,45].…”

“…employed in a recurrent neural network that self-organises into a balanced state [42] has 105 been shown recently to exist in auditory cortex [26]. Besides the symmetric iSTDP…”