Strong preference for autaptic self-connectivity of neocortical PV interneurons entrains them to γ-oscillations

Charlotte Deleuze, Gary S Bhumbra, Antonio Pazienti, Caroline Mailhes, Andrea Aguirre, Marco Beato, Alberto Bacci

Preprint posted on 1 December 2018

Article now published in PLOS Biology at

A team effort by the Bacci and Beato labs sheds light on the detailed organization of inhibitory autapses in neocortical interneurons.

Selected by Mahesh Karnani

Categories: biophysics, neuroscience


A team effort by the Bacci and Beato labs sheds light on the detailed organization of inhibitory autapses in neocortical interneurons.



Autapses are synapses formed by a neuron onto itself, and this is something that happens most frequently in neocortical parvalbumin (PV) containing fast spiking interneurons 1–3. Not many studies have focused on autapses 4, but from the few that have it seems PV cell autapses can either synchronize spiking 1 or, after firing at high-frequency, desynchronize it through long-lasting self-inhibition 5. The role of PV cell autapses remains elusive 6.


Key findings

This study from two extremely competent synaptic physiology labs shows that the autapses on these cells are surprisingly strong, constituting up to 40% of the total inhibitory input. The autapses were stronger than other inhibitory synapses formed by the cells onto nearby pyramidal neurons. The authors used Bayesian quantal analysis to show the autaptic strength was higher than PV->pyramidal synapses due to bigger quantal size (i.e., bigger postsynaptic response to a released synaptic vesicle), while PV->PV synapses had similar quantal size as the autapses. The autapses had varying strength relative to heterosynaptic PV->PV synapses formed by the same presynaptic cell and this was due to different numers of presynaptic release sites. Some PV cells had stronger autaptic connections than heterosynaptic PV->PV synapses. These were termed introverted cells. Some PV cells had the opposite arrangement of synaptic strength and were termed extroverted cells. The authors went on to demonstrate that during optogenetically induced network oscillations, the transient self-inhibitory influence of PV cell autapses phases their action potential firing into the gamma-frequency range (~30Hz) rather than inhibiting themselves over a longer period. This is an important demonstration of a potential role for autapses, as previous work has shown that PV cell autapses can also elicit a prolonged asynchronous self inhibition after high frequency burst activity 5.

Introverted PV neurons inhibit themselves more than other PVs while extroverted PVs do the opposite. Taken with permission from figure 3 in Deleuze et al 2018


Why I chose this preprint 

This is an important study because it uncovers a new functional organization of these interneurons into subtypes defined by connectivity: introverted and extroverted PV cells. Anatomically, PV cells have a moderate tendency to form clusters where they are packed near each other more densely 7–10. In vivo recordings of small samples of PV cells (which could have been within a cluster) have shown them to be highly coactive with each other 11. If all cortical PV cells are not simultaneously active, one possibility is that anatomical PV cell clusters form functionally coactive teams. In this case extroverted PV cells might be located on the borders or outside the clusters while introverted PV neurons would be at the core of the team. This way the introverts could keep a stronger rhythm without interfering with other nearby team members while extroverts at the border would compete against other PV teams and delineate a functional boundary. It would be interesting to see how intersomatic distance metrics from the authors’ recordings square up to this hypothesis.


What next?

Besides autapses, another key factor controlling PV neuron synchronization is their electrical coupling with each other. It would be interesting to see if electrical coupling is higher among neighbouring introverts than extroverts. As divergent excitatory input from shared presynaptic principal neurons is common among PV neurons, it would also be interesting to study whether introverts and extroverts are part of different excitatory subnetworks.

A major question for the future is whether PV cell autapses are plastic 6. This could provide the rationale for a neuron to use such a complicated mechanism to self-regulate (let’s face it, self-inhibition could conceivably be done by increased voltage gated potassium channels for example to achieve a stronger after-hyperpolarization). If the plasticity of autapses can achieve something special, such as automatically tuning the cell to an impinging rhythm, this could offer a profound explanation for these mysterious cables.



  1. Bacci, A. & Huguenard, J. R. Enhancement of spike-timing precision by autaptic transmission in neocortical inhibitory interneurons. Neuron 49, 119–30 (2006).
  2. Bacci, A., Huguenard, J. R. & Prince, D. A. Functional autaptic neurotransmission in fast-spiking interneurons: a novel form of feedback inhibition in the neocortex. J. Neurosci. 23, 859–66 (2003).
  3. Tamás, G., Buhl, E. H. & Somogyi, P. Massive autaptic self-innervation of GABAergic neurons in cat visual cortex. J. Neurosci. 17, 6352–64 (1997).
  4. Ikeda, K. & Bekkers, J. M. Autapses. Curr. Biol. 16, R308 (2006).
  5. Manseau, F. et al. Desynchronization of Neocortical Networks by Asynchronous Release of GABA at Autaptic and Synaptic Contacts from Fast-Spiking Interneurons. PLoS Biol. 8, e1000492 (2010).
  6. Deleuze, C., Pazienti, A. & Bacci, A. Autaptic self-inhibition of cortical GABAergic neurons: Synaptic narcissism or useful introspection? Curr. Opin. Neurobiol. 26, 64–71 (2014).
  7. Wang, X. et al. Three-dimensional intact-tissue sequencing of single-cell transcriptional states. Science 361, eaat5691 (2018).
  8. Amitai, Y. et al. The spatial dimensions of electrically coupled networks of interneurons in the neocortex. J. Neurosci. 22, 4142–52 (2002).
  9. Karnani, M. M. & Jackson, J. Interneuron Cooperativity in Cortical Circuits. Neuroscientist 24, 329–341 (2018).
  10. Ebina, T. et al. 3D Clustering of GABAergic Neurons Enhances Inhibitory Actions on Excitatory Neurons in the Mouse Visual Cortex. Cell Rep. 9, 1896–1907 (2014).
  11. Hofer, S. B. et al. Differential connectivity and response dynamics of excitatory and inhibitory neurons in visual cortex. Nat. Neurosci. 14, 1045–52 (2011).


Tags: autapse, gamma oscillation, inhibition, parvalbumin interneuron

Posted on: 20 December 2018 , updated on: 21 December 2018


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