Professor, Biological Sciences
My research focuses on the cellular and molecular mechanisms underlying synaptic plasticity in the nervous system. Changes at the synaptic level occur both during development and as a result of experience, in the form of learning and memory. Studying such changes in synaptic connections help us to understand how alterations in the brain relate to changes at the behavioural level.
In my laboratory, the research falls into two general areas:
1.the study of interactions between neurons regenerating in culture, and
2. investigation of the cellular mechanisms of learning and memory.
In both of these areas of study, we utilize the mollusc, Lymnaea stagnalis.
- Many neurons in the brain of Lymnaea are large, identifiable from one brain to the next, and their transmitters and synaptic connections have been described. When removed from the brain, they regenerate neurites in cell culture. At the end of each neurite is a growing tip known as the growth cone. These growth cones use signals in their environment to guide the growing processes to their appropriate targets. My studies investigate what signals may act on these growth cones and aim to determine how and why the growth cones respond in a specific manner.
- Operant conditioning is a form of associative learning commonly used by humans, and is a response-dependent form of learning (reward or punishment paradigm). Unlike classical conditioning, the cellular mechanisms underlying operant conditioning are not well understood. Using the respiratory behaviour of Lymnaea, we can operantly condition the animal and investigate at the level of single identified neurons and their specific connections, what cellular changes occur during both learning and memory.
We are currently studying the role of the Vitamin A metabolite, retinoic acid, in its ability to both guide regenerating neurites as well as to affect learning and memory in Lymnaea stagnalis.
Our research has shown that retinoic acid can induce growth cone turning of regenerating neurites of Lymnaea central neurons. This growth cone turning can also occur in transected neurites, isolated from their cell bodies, indicating that this is a localized effect, independent of gene transcription. Indeed, we have evidence to indicate that retinoic acid-mediated growth cone turning requires local protein synthesis as well as calcium influx. Our current research (in collaboration with R. Carlone at Brock) continues to investigate the cellular and molecular mechanisms involved in retinoic acid-mediated growth cone turning.
In addition to its effects on neuronal development and regeneration, retinoic acid is also known to play an important role in the adult brain, during learning and memory. We have determined that retinoic acid is required for long-term memory formation (but not learning) in Lymnaea, indicating that it may exert similar effects in some invertebrates, as in vertebrates. Our current research aims to examine the cellular changes within the defined circuits of the CNS that are affected by retinoic acid and hence are important for memory consolidation.
BSc (Hons), Physiology, 1990. University of Leeds, UK.
PhD Physiology,1993. University of Leeds, UK
- Wingrove J, de Hoog E, Spencer GE (2023). Disruptions in network plasticity precede deficits in memory following inhibition of retinoid signaling. Journal of Neurophysiology. 129: 41-55.
- de Hoog E, Spencer GE (2022). Activity-dependent modulation of neuronal KV channels by retinoic acid enhances CaV channel activity. Journal of Biological Chemistry. 298(6): 101959..
- de Hoog E, Saba Echezarretta VE, Turgambayeva A, Foran G, Megaly M, Necakov A, Spencer GE (2022). Molluscan RXR transcriptional regulation by retinoids in a Drosophila CNS organ culture system. Cells. 11: 2493.
- Piekut T^, Wong YY^, Walker S^, Smith CL^, Gauberg J, Harracksingh A, Lowden C, Cheng H-Y M, Spencer GE, Senatore, A. (2020). Early metazoan origin and multiple losses of a novel clade of RIM presynaptic calcium channel scaffolding protein homologues. (with COVER IMAGE). Genome Biology and Evolution; doi: 10.1093/gbe/eva (^ these authors contributed equally).
- Walker SE, Senatore A, Carlone RL, Spencer GE. (2020). Context-dependent role of miR-124 in retinoic acid-induced growth cone attraction of regenerating motorneurons. Cellular and Molecular Neurobiology. DOI 10.1007/s10571-020-00982-4.
- de Hoog E, Lukewich MK, Spencer GE. (2019). Retinoid receptor-based signaling plays a role in voltage-dependent inhibition of invertebrate voltage-gated Ca2+ channels. Journal of Biological Chemistry. 294(26): 10076-10093.
- Johnson A, Nasser T, Spencer GE. (2019) Inhibition of Rho GTPases Induces a Switch in Growth Cone Responsiveness to Retinoic Acid. Biomolecules Sep 7; 9(9).(Invited; Special Edition on Retinoids).
- Johnson A, de Hoog E, Tolentino M, Nasser T, Spencer GE. (2019) Pharmacological evidence for the role of RAR in axon guidance and embryonic development of a protostome species.
Genesis. 2019 Jul;57(7-8):e23301. doi: 10.1002/dvg.23301. Epub 2019 Apr 30.
- de Hoog E, Lukewich M, Spencer GE. (2019) Retinoid receptor-based signaling plays a role in voltage-dependent inhibition of invertebrate voltage-gated Ca2+ channels. J. Biol. Chem 294(26): 10076-10093. doi: 10.1074/jbc.RA118.006444
- Walker S, Spencer G, Necakov A and Carlone, R. (2018). Identification and Characterization of microRNAs during Retinoic Acid-Induced Regeneration of a Molluscan Central Nervous System. Int J Mol Sci. 19(9). doi: 10.3390/ijms19092741
- Rothwell CM, Spencer GE, Lukowiak K. (2018). The effect of rearing environment on memory formation. Journal of Experimental Biology 221(Pt 10). pii: jeb180521. doi: 10.1242/jeb.180521.
- Walker, S. Carter, C. Nottrodt, R. Spencer, GE, Carlone, RL. (2018). RXRα downregulation is required for tail and caudal spinal cord regeneration in the adult newt. Neural Regeneration Research: 13(6):1036-1045
- de Hoog E, Lukewich M, Spencer GE (2018). Retinoic acid inhibits neuronal voltage-gated calcium channels. Cell Calcium 72: 51-61.
- Rand C, Spencer GE, Carlone R. (2017). Retinoic acid as a chemoattractant for embryonic spinal cord neurons of Xenopus laevis. Canadian Journal of Zoology 95:653-661.
- Rothwell CM deHoog E Spencer GE (2017). The role of retinoic acid in the formation and modulation of invertebrate central synapses. Journal of Neurophysiology 117(2):692-704.
- Carpenter S, Rothwell CM, Wright, M. de Hoog E, Walker S, Hudson E, Spencer GE. (2016). Extending the duration of long-term memories: interactions between environmental darkness and retinoid signaling. Neurobiology of Learning and Memory 136:34-46
- Vesprini ND, Dawson TF, Yuan Y, Bruce D, Spencer GE (2015). Retinoic acid affects calcium signaling in adult molluscan neurons. Journal of Neurophysiology 113(1):172-81.
- Carter C, Rand C, Mohammad I, Lepp A, Vesprini N, Wiebe O, Carlone R, Spencer GE (2015) Expression of a retinoic acid receptor (RAR)-like protein in the embryonic and adult nervous system of a protostome species. Journal of Experimental Zoology B Mol Dev Evol. 324(1):51-67
- Rothwell C, Simmons J, Peters G, Spencer GE (2014) Novel interactive effects of darkness and retinoid signaling in the ability to form long-term memory following aversive operant conditioning. Neurobiology of Learning and Memory 114: 251-263
- Rothwell C, Spencer GE (2014) Retinoid signaling is necessary for, and promotes long-term memory formation following operant conditioning. Neurobiology of Learning and Memory. 114: 127-140
- Vesprini N, Spencer GE (2014) Retinoic acid induces changes in electrical properties of adult neurons, in a dose-and isomer-dependent manner. Journal of Neurophysiology Mar; 111(6):1318-30.
- Spencer GE and Rothwell C (2013) Behavioural and network plasticity following conditioning of the aerial respiratory response of a pulmonate mollusc. Canadian Journal of Zoology; Special edition: Trends in the biology of the phylum Mollusca June, 91(6). 382-390.
- Szuroczki D, Vesprini, ND, Jones, TRB, Spencer, GE, Carlone (2012). Presence of Ribeiroia ondatrae in the developing anuran limb disrupts retinoic acid levels. Parasitology Research Jan; 110(1):49-59.
- Carter C, Clark A, Spencer G, Carlone R (2011). Cloning and expression of a retinoic acid receptor β2 subtype from the adult newt: Evidence for an early role in tail and caudal spinal cord regeneration. Developmental Dynamics Dec; 240:2613-2625.
- Carter CJ, Farrar N, Carlone RL, Spencer GE (2010). Developmental expression of a molluscan RXR and evidence for its novel, non-genomic role in growth cone guidance. Developmental Biology. July; 343:124-37
- Farrar N, Dmetricuk JM, Carlone RL, Spencer GE (2009) A novel, non-genomic mechanism underlies retinoic acid-induced growth cone turning. Journal of Neuroscience Nov; 29(45):14136-42.
- Feng ZP, Zhang Z, van Kesteren RE, Straub VA, van Nierop P, Jin, K., Nejatbakhsh N, Goldberg JI, Spencer GE, Yeoman MS, Wildering W, Coorssen JR, Croll RP, Buck L, Syed NI, Smit AB (2009). Transcriptome analysis of the central nervous system of the mollusc. Lymnaea stagnalis. BMC Genomics Sept; 10:451
- Khan AM, Spencer GE (2009) Novel neural correlates of operant conditioning in normal and differentially reared Journal of Experimental Biology Apr; 212: 922-933.
- Farrar NR, Spencer GE (2008). In pursuit of a turning point in growth cone research. Developmental Biology June; 318: 102-111.
- Dmetrichuk JM, Carlone RL, Jones TRB, Vesprini N, Spencer GE (2008). Detection of endogenous retinoids in the molluscan CNS and characterization of the trophic and tropic actions of 9-cis retinoic acid on isolated neurons. Journal of Neuroscience Nov; 28(48):13014-13024.
- Dobson K, Dmetrichuk JM and Spencer GE (2006). Different receptors mediate the electrophysiological and growth cone responses of identified neurons to applied dopamine. Neuroscience 141:1801-1810.
- Dmetrichuk J, Carlone R and Spencer G (2006) Retinoic acid induces neurite outgrowth and growth cone turning in invertebrate neurons. Developmental Biology 294:39-49.
- van Kesteren RE Carter C, Dissel HMG, van Minnen J, Gouwenberg Y, Syed NI, Spencer GE, and Smit AB (2006). Local synthesis of actin-binding protein b-thymosin regulates neurite outgrowth. Neurosci. 26: 152-157
- Lowe MR and Spencer GE. (2006) Perturbation of the Activity of a Singled Identified Neuron Affects Long-Term Memory Formation in a Molluscan Semi-intact Preparation. Journal of Experimental Biology 209: 711-721.
Distinguished Research Award (2018)
Awarded by Faculty of Mathematics and Science, Brock University, for outstanding research achievements.