The recovery paper has come out

Finally, my "recovery paper" came out:

Recruitment of polysynaptic connections underlies functional recovery of a neural circuit after lesion.

Akira Sakurai, Arianna N. Tamvacakis, Paul S. Katz

DOI: 10.1523/ENEURO.0056-16.2016

This paper shows that, when a neural circuit failed by losing one of its synapses within, functional recovery can occur through reorganization of the remaining neural circuitry. We show that a molluscan neural circuit recruits additional neurons in response to a lesion. The extent of recruitment predicts the extent of behavioral recovery. 

Even in a well-defined (sort of) invertebrate neural circuit, there are indirect, polysynaptic pathways that provide compensatory function or flexibility to the circuit. Such individual variability appears to be hidden under normal conditions but becomes relevant when challenged by neural injury.

This paper is a sequel of two preceding papers:

Functional Recovery after Lesion of a Central Pattern Generator (2009)

Hidden synaptic differences in a neural circuit underlie differential behavioral susceptibility to a neural injury (2014)

Variability, compensation and homeostasis in neuron and network function

Eve Marder and Jean-Marc Goaillard

Hebbian learning can be appropriately balanced by stability mechanisms that allow neurons and synaptic connections to be maintained in appropriate operating ranges (by Turrigiano and Nelson, various mechanisms including synaptic scaling and changes in individual ionic currents).

omeostatic tuning rules that maintain a constant activity pattern could, in principle, operate to tune conductances so that an individual neuron remains within a given region of parameter space, although its values for one or more conductances may be substantially
altered.

Variability in channel densities
How can we reconcile the apparent sensitivity of many neurons to rapid pharmacological treatments with new data indicating that individual neurons within a class can differ by as much as two- to fourfold in the densities of many of their currents?
Computational models show that a number of different compensating combinations of conductances can result in similar activity patterns38,51.

In contrast to pharmacological manipulations, slow mechanisms that function during development and over days and weeks can result in a set of compensating conductances that give rise to a target activity pattern.

Figure 2 | Neurons with similar intrinsic properties have different ratios of conductances.

Figure 3 | Comparison of short-term pharmacological manipulations and long-term genetic deletions.

Slow developmental and homeostatic mechanisms can ‘find’ multiple solutions of correlated
and compensating values of membrane conductances consistent with a given activity pattern, even while rapid pharmacological treatments that vary the value of one current at a time result in altered activity57.

Homeostatic synapse-driven membrane plasticity in nucleus accumbens neurons

By Ishikawa,M.; Mu,P.; Moyer,J.T.; Wolf,J.A.; Quock,R.M.; Davies,N.M.; Hu,X.T.; Schluter,O.M.; Dong,Y.


Abstract:
- Homeostatic mechanisms balances the input-output/synapse-membrane interaction at nucleus accumbens neurons.
- Studies on nucleus accumbens (NAc) neurons revealed a novel form of synapse-to-membrane homeostatic regulation (hSMP), homeostatic synapse-driven membrane plasticity (hSMP).
- Through hSMP, NAc neurons adjusted their membrane excitability to functionally compensate for basal shifts in excitatory synaptic input.
- hSMP is triggered by synaptic NMDA receptors.

Introduction:- Homeostatic plasticity is an important cellular mechanism through which neurons use the neuroplasticity mechinery to maintain stable functional output in an ever-changing internal and external environment (Turrigiano and Nelson, 2004).
- The functional output of a neuron relies on dynamic integration of synaptic inputs and intrinsic membrane excitability.
- It has long been known that homeostatic plasticity can occur independently at either synapses (Turrigiano and Nelson, 2004) or the membrane excitability (Zhang and Linden, 2003).

Results:
- hSMP in NAc slice cultures: NAc mediam spiny neuron (MSNs) increased excitability in slice culture.
- NMDA receptor mediates hSMP. DCS (D-cycloserine).
- hSMP in acute brain slices.
- Synapse-specific hSMP.
- SK channels mediate the expression of hSMP.
- Implication of hSMP in cocaine -induced membrane adaptation.