Experience-dependent homeostasis of ‘noise’ at inhibitory synapses preserves information coding in adult visual cortex

Abstract

Synapses are intrinsically 'noisy' in that neurotransmitter is occasionally released in the absence of an action potential. At inhibitory synapses, the frequency of action potential-independent release is orders of magnitude higher than that at excitatory synapses raising speculations that it may serve a function. Here we report that the frequency of action potential-independent inhibitory synaptic 'noise' (i.e. miniature inhibitory postsynaptic currents, mIPSCs) is highly regulated by sensory experience in visual cortex. Importantly, regulation of mIPSC frequency is so far the predominant form of functional plasticity at inhibitory synapses in adults during the refractory period for plasticity and is a locus of rapid non-genomic actions of oestrogen. Models predict that regulating the frequency of mIPSCs, together with the previously characterized synaptic scaling of miniature excitatory PSCs, allows homeostatic maintenance of both the mean and variance of inputs to a neuron, a necessary feature of probabilistic population codes. Furthermore, mIPSC frequency regulation allows preservation of the temporal profile of neural responses while homeostatically regulating the overall firing rate. Our results suggest that the control of inhibitory 'noise' allows adaptive maintenance of adult cortical function in tune with the sensory environment.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.

Integrating Hebbian and homeostatic plasticity: the current state of the field and future research directions

“…Changes in inhibitory tone may be modulated via astrocytes [35] or NMDA receptor input [36]. Changing the activity of inhibitory neurons provides an important homeostatic mechanism by which activity levels can be rapidly (within seconds) adjusted through the increase or the decrease in the firing rate of inhibitory neurons to prevent short-term increases in activity levels that would be associated with pathological activity such as seizures; however, recent work suggests that minimizing changes to inhibition helps maintain temporal coding in the network, which is shaped by the inhibitory circuit [37], so some maintenance of inhibitory tone is likely essential for the circuit. Adjusting synaptic strength or neuronal excitability occurs over much longer time courses of hours [6], which would be much too slow to account for activity peaks that would potentially cause pathological over-excitation.…”

Endocannabinoid Signaling Contributes to Experience-Induced Increase of Synaptic Release Sites From Parvalbumin Interneurons in Mouse Visual Cortex

“…Finally, it is worth pointing out that from a functional point of view, increases in release sites without changes in release probability could be a way to strengthen inhibitory output without altering the dynamic properties of release, which in the case of PV-INs, are uniquely tuned to maintain the performance over a wide range of firing activity (Bridi et al, 2020b). In turn, this idea concords with the notion of a need for mechanisms that change overall network inhibition without compromising the temporal dynamics of synaptic inhibition (Gao et al, 2017).…”

“…Acute visual cortical slices (300 µm) from G42 mice were prepared as previously described (Jiang et al, 2010b;Gu et al, 2013;Huang et al, 2013;Gao et al, 2017;Bridi et al, 2020b). Briefly, slices were cut in the ice-cold dissection buffer containing (in mM): 212.7 sucrose, 5 KCl, 1.25 NaH 2 PO 4 , 10 MgCl 2 , 0.5 CaCl 2 , 26 NaHCO 3 , 10 dextrose, bubbled with 95% O 2 /5% CO 2 (pH 7.4).…”

“…Two types of internal solution were used for dual-patch clamp in this study: a K-based internal solution (in mM: 130 KGluconate, 10 KCl, 0.2 EGTA, 10 HEPES, 0.5 NaGTP, 4 MgATP, and 10 Na 2 -Phosphocreatine; pH adjusted to 7.25 with KOH, 280-290 mOsm), and a CsCl-based internal solution (in mM: 120 CsCl, 8 NaCl, 10 HEPES, 2 EGTA, 5 QX-314, 0.5 Na 2 GTP, 4 MgATP, and 10 Na 2 -Phosphocreatine; pH adjusted to 7.25 with CsOH, 280-290 mOsm). As previously described (Jiang et al, 2010b;Gu et al, 2013;Huang et al, 2013;Gao et al, 2017;Bridi et al, 2020b), in the layer 2/3 of the visual cortex, PV-INs were identified by fluorescence and recorded under current clamp with pipettes containing the K-based internal solution. Pyramidal cells were visually identified by their pyramidal looking soma and clear apical dendrite (Jiang et al, 2007) and recorded under voltage clamp with pipettes filled with the CsCl-based internal solution.…”

Co-opting evo-devo concepts for new insights into mechanisms of behavioural diversity

“…Simulated gene regulatory networks with greater plasticity are more sensitive to the effects of mutations, harbour greater genetic variance, and have different evolutionary trajectories than non-plastic gene networks (Draghi and Whitlock, 2012). The activity-dependent homeostatic mechanisms that tune synaptic plasticity to preserve neural network stability and support ongoing plasticity (Tetzlaff et al, 2011;Gao et al, 2017;Zenke and Gerstner, 2017) have not been considered in the context of genetic variation. Thus we lack information about how variation in neural circuit plasticity might impact behavioural reliability, performance and evolvability.…”