David Roderick Curtis. 3 June 1927—11 December 2017

David Curtis was a pioneer in the identification of excitatory and inhibitory transmitters released at synapses in the central nervous system. He made major contributions to the identification of gamma-amino butyric acid (GABA) and glycine as inhibitory transmitters released at inhibitory synapses. His work laid the foundation for the subsequent acceptance that l -glutamate was the major excitatory transmitter. David's scientific work led to him receiving many accolades and honours, including fellowships of the Australian Academy of Sciences and the Royal Society and a Companion of the Order of Australia. Note: This memoir was commissioned by the Historical Records of Australian Science and is published here with minor amendments. It was published in June 2020 and is available at https://doi.org/10.1071/HR19016 .

David Roderick Curtis 1927–2017

David Curtis was a pioneer in the identification of excitatory and inhibitory transmitters released at synapses in the central nervous system. He made major contributions to the identification of gamma-amino butyric acid (GABA) and glycine as inhibitory transmitters released at inhibitory synapses. His work laid the foundation for the subsequent acceptance that L-glutamate was the major excitatory transmitter. David’s scientific work led to him receiving many accolades and honours, including Fellowships of the Australian Academy of Sciences, the Royal Society and a Companion of the Order of Australia.

Neuroprotection Against Hypoxic/Ischemic Injury: δ-Opioid Receptors and BDNF-TrkB Pathway

The delta-opioid receptor (DOR) is one of three classic opioid receptors in the opioid system. It was traditionally thought to be primarily involved in modulating the transmission of messages along pain signaling pathway. Although there were scattered studies on its other neural functions, inconsistent results and contradicting conclusions were found in past literatures, especially in terms of DOR’s role in a hypoxic/ischemic brain. Taking inspiration from the finding that the turtle brain exhibits a higher DOR density and greater tolerance to hypoxic/ischemic insult than the mammalian brain, we clarified DOR’s specific role in the brain against hypoxic/ischemic injury and reconciled previous controversies in this aspect. Our serial studies have strongly demonstrated that DOR is a unique neuroprotector against hypoxic/ischemic injury in the brain, which has been well confirmed in current research. Moreover, mechanistic studies have shown that during acute phases of hypoxic/ischemic stress, DOR protects the neurons mainly by the stabilization of ionic homeostasis, inhibition of excitatory transmitter release, and attenuation of disrupted neuronal transmission. During prolonged hypoxia/ischemia, however, DOR neuroprotection involves a variety of signaling pathways. More recently, our data suggest that DOR may display its neuroprotective role via the BDNF-TrkB pathway. This review concisely summarizes the progress in this field.

PKC-mediated GABAergic enhancement of dopaminergic responses: implication for short-term potentiation at a dual-transmitter synapse

Transmitter-mediated homosynaptic potentiation is generally implemented by the same transmitter that mediates the excitatory postsynaptic potentials (EPSPs), e.g., glutamate. When a presynaptic neuron contains more than one transmitter, however, potentiation can in principle be implemented by a transmitter different from that which elicits the EPSPs. Neuron B20 in Aplysia contains both dopamine and GABA. Although only dopamine acts as the fast excitatory transmitter at the B20-to-B8 synapse, GABA increases the size of these dopaminergic EPSPs. We now provide evidence that repeated stimulation of B20 potentiates B20-evoked dopaminergic EPSPs in B8 apparently via a postsynaptic mechanism, and short-term potentiation of this synapse is critical for the establishment and maintenance of an egestive network state. We show that GABA can act postsynaptically to increase dopamine currents that are elicited by direct applications of dopamine to B8 and that dopamine is acting on a 5-HT3-like receptor. This potentiation is mediated by GABAB-like receptors as GABAB-receptor agonists and antagonists, respectively, mimicked and blocked the potentiating actions of GABA. The postsynaptic actions of GABA rely on a G protein-mediated activation of PKC. Our results suggest that the postsynaptic action of cotransmitter-mediated potentiation may contribute to the maintenance of the egestive state of Aplysia feeding network and, in more general terms, may participate in the plasticity of networks that mediate complex behaviors.

Lactate-mediated glia-neuronal signalling in the mammalian brain

Astrocytes produce and release L-lactate as a potential source of energy for neurons. Here we present evidence that L-lactate, independently of its caloric value, serves as an astrocytic signalling molecule in the locus coeruleus (LC). The LC is the principal source of norepinephrine to the frontal brain and thus one of the most influential modulatory centers of the brain. Optogenetically activated astrocytes release L-lactate, which excites LC neurons and triggers release of norepinephrine. Exogenous L-lactate within the physiologically relevant concentration range mimics these effects. L-lactate effects are concentration-dependent, stereo-selective, independent of L-lactate uptake into neurons and involve a cAMP-mediated step. In vivo injections of L-lactate in the LC evokes arousal similar to the excitatory transmitter, L-glutamate. Our results imply the existence of an unknown receptor for this ‘glio-transmitter’.