University Lecturer in Neuropharmacology
Dr Akerman’s group is examining the principles underlying synaptic circuit formation and plasticity. The group’s work combines electrophysiological assessment of synaptic transmission, single and multi-photon confocal imaging of neurons, and molecular-genetic techniques to both observe and manipulate synaptic circuit development and plasticity.
The group is exploring three areas:
- How do neurons select their synaptic partners?
- How are synaptic circuits affected by activity-dependent processes?
- How do neurons integrate excitatory and inhibitory synaptic inputs?
The type, strength, and distribution of synaptic connections determine the behavior of individual neurons within a neural network. For instance, experimental and computational modeling data demonstrate that the pattern of excitatory (glutamatergic) and inhibitory (GABAergic) synaptic inputs across the dendritic tree dictates how information is integrated and stored. These synaptic circuits develop through a combination of ‘hard-wired’ genetic mechanisms and ‘plastic’ activity-dependent processes. Understanding this interplay underlies many of the projects in Dr Akerman’s group. For example, the group is interested in establishing how the connectivity of an individual neuron becomes restricted during its development. But equally, how do activity-dependent processes enable a neuron to adjust the weights of its synaptic connections in the appropriate way? This is particularly relevant during development, when the external environment is known to shape neuronal response properties and mechanisms that control synaptic strength are sensitive to the spatiotemporal patterns of neural activity. A related question is how neurons establish and maintain the correct arrangement of excitatory and inhibitory synaptic inputs. The major inhibitory neurotransmitter in the mature brain is GABA. During development however, and interestingly also in epilepsy, GABA can exert excitatory effects. This results from changes in intracellular chloride, which alters the driving force on chloride permeable GABAA receptors. Dr Akerman’s group are examining how such a fundamental shift in GABAergic signaling influences ongoing network activity and activity-dependent processes.
Neuronal Chloride Regulation via KCC2 Is Modulated through a GABAB Receptor Protein Complex.
Wright R. et al, (2017), J Neurosci, 37, 5447 - 5462
Mapping neurogenesis onset in the optic tectum of Xenopus laevis.
Herrgen L. and Akerman CJ., (2016), Dev Neurobiol, 76, 1328 - 1341
Random synaptic feedback weights support error backpropagation for deep learning.
Lillicrap TP. et al, (2016), Nat Commun, 7
Tight Coupling of Astrocyte pH Dynamics to Epileptiform Activity Revealed by Genetically Encoded pH Sensors.
Raimondo JV. et al, (2016), J Neurosci, 36, 7002 - 7013
Assessing similarity to primary tissue and cortical layer identity in induced pluripotent stem cell-derived cortical neurons through single-cell transcriptomics.
Handel AE. et al, (2016), Hum Mol Genet, 25, 989 - 1000