Many theories of brain function assume that information is encoded and behaviour is controlled through sparse, distributed patterns of activity. It is therefore crucial to place a lower bound on the amount of neural activity that can drive behaviour and to understand how neuronal networks operate within these constraints. We use an all-optical approach to test this lower limit by driving behaviour with targeted two-photon optogenetic activation of small ensembles of L2/3 pyramidal neurons in mouse barrel cortex while using two-photon calcium imaging to record the impact on the local network. By precisely titrating the number of neurons in activated ensembles we demonstrate that the lower bound for detection of cortical activity is ~14 pyramidal neurons. We show that there is a very steep sigmoidal relationship between the number of activated neurons and behavioural output, saturating at only ~37 neurons, and that this relationship can shift with learning. By simultaneously measuring activity in the local network, we show that the activation of stimulated ensembles is balanced by the suppression of neighbouring neurons. This surprising behavioural sensitivity in the face of potent network suppression supports the sparse coding hypothesis and suggests that perception of cortical activity balances a trade-off between minimizing the impact of noise while efficiently detecting relevant signals.
Import, processing, analysis and figure code is available on Github (Dalgleish, 2020; https://github.com/alloptical/Dalgleish-eLife-2020) for use with analysed data (https://doi.org/10.6084/m9.figshare.13135505) and/or unprocessed behavioural session data (https://doi.org/10.6084/m9.figshare.13128950). Raw calcium imaging movies are ~1TB in size and are thus available upon reasonable request.
How many neurons are sufficient for perception of cortical activity?Figshare, https://doi.org/10.6084/m9.figshare.13128950; https://doi.org/10.6084/m9.figshare.13135505.
- Michael Häusser
- Michael Häusser
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All experimental procedures were carried out under Project Licence 70/14018 (PCC4A4ECE) issued by the UK Home Office in accordance with the UK Animals (Scientific Procedures) Act (1986) and were also subject to local ethical review. All surgical procedures were carried out under isoflurane anaesthesia (5% for induction, 1.5% for maintenance), and every effort was made to minimize suffering.
- Brice Bathellier, CNRS, France
© 2020, Dalgleish et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
The presynaptic protein α-synuclein (αSyn) has been suggested to be involved in the pathogenesis of Parkinson’s disease (PD). In PD, the amygdala is prone to develop insoluble αSyn aggregates, and it has been suggested that circuit dysfunction involving the amygdala contributes to the psychiatric symptoms. Yet, how αSyn aggregates affect amygdala function is unknown. In this study, we examined αSyn in glutamatergic axon terminals and the impact of its aggregation on glutamatergic transmission in the basolateral amygdala (BLA). We found that αSyn is primarily present in the vesicular glutamate transporter 1-expressing (vGluT1+) terminals in mouse BLA, which is consistent with higher levels of αSyn expression in vGluT1+ glutamatergic neurons in the cerebral cortex relative to the vGluT2+ glutamatergic neurons in the thalamus. We found that αSyn aggregation selectively decreased the cortico-BLA, but not the thalamo-BLA, transmission; and that cortico-BLA synapses displayed enhanced short-term depression upon repetitive stimulation. In addition, using confocal microscopy, we found that vGluT1+ axon terminals exhibited decreased levels of soluble αSyn, which suggests that lower levels of soluble αSyn might underlie the enhanced short-term depression of cortico-BLA synapses. In agreement with this idea, we found that cortico-BLA synaptic depression was also enhanced in αSyn knockout mice. In conclusion, both basal and dynamic cortico-BLA transmission were disrupted by abnormal aggregation of αSyn and these changes might be relevant to the perturbed cortical control of the amygdala that has been suggested to play a role in psychiatric symptoms in PD.
Animals can evolve dramatic sensory functions in response to environmental constraints, but little is known about the neural mechanisms underlying these changes. The Mexican tetra, Astyanax mexicanus, is a leading model to study genetic, behavioral, and physiological evolution by comparing eyed surface populations and blind cave populations. We compared neurophysiological responses of posterior lateral line afferent neurons and motor neurons across A. mexicanus populations to reveal how shifts in sensory function may shape behavioral diversity. These studies indicate differences in intrinsic afferent signaling and gain control across populations. Elevated endogenous afferent activity identified a lower response threshold in the lateral line of blind cavefish relative to surface fish leading to increased evoked potentials during hair cell deflection in cavefish. We next measured the effect of inhibitory corollary discharges from hindbrain efferent neurons onto afferents during locomotion. We discovered that three independently derived cavefish populations have evolved persistent afferent activity during locomotion, suggesting for the first time that partial loss of function in the efferent system can be an evolutionary mechanism for neural adaptation of a vertebrate sensory system.