Research


We use laboratory rats to study the psychological processes and neural mechanisms involved in learning and memory. 

The Neural Substrates of Higher-Order Conditioned Fear

Rats and people learn to fear cues that signal innate sources of danger, e.g., pain, as well as cues that signal learned sources of danger, e.g., the sound of gunfire. Pavlov (1927) termed the former type of learning, first-order conditioning, and the latter type second-order conditioning.

Both types of fear depend on the amygdala but their molecular signatures are different. This project examines the nature of these differences: specifically, the interaction between gene transcription and protein synthesis in consolidation of the two types of fear, including the epigenetic mechanisms that mediate that interaction (DNA methylation, histone acetylation).

False Memories In Laboratory Rodents

Memory is not perfect. One of its flaws is that we remember events that did not happen or did not happen in the way in which we remember them. The aim of this project is to identify the brain substrates underling the formation, storage and retrieval of false memories. The project takes advantage of a behavioural protocol that we have recently developed to generate a false context fear memory in rodents. It employs this protocol to determine the conditions under which the false memory occurs and uses genetic tools and contemporary neuroscience techniques to establish the neural substrates of the false memory.

Oxytocin Impairs Fear Acquisition and Fear Inhibition: Mechanisms of Action in the Basolateral Complex of the Amygdala


Anxiety disorders such as post-traumatic stress originate in one or more traumatic experiences which imbue cues present the at trauma with the ability to trigger flashbacks, fear and avoidance.

Clinical trials have shown that cognitive-behavioural therapy (CBT) is more effective in the long-term treatment of this disorder than other forms of therapy. A component of CBT is cue exposure in which the sufferer, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. The aim of these confrontations is to extinguish the ability of the trauma-related cues to trigger the flashbacks, the fear and the avoidance that undermine the quality of the sufferer's life. This aim is frequently achieved but relapse also occurs. Hence, there is a need to develop more effective ways of extinguishing the effects of trauma-related cues.

This project uses a rodent model to examine whether oxytocin is one such way. Previous work has shown that activation of oxytocin receptors in the amygdala (a region of the brain known to be involved in emotional learning, including fear) impairs the development of learned fear and enhances extinction of such fear. The project uses a range of neuroscience techniques to understand how oxytocin affects the amygdala to impair fear learning and facilitate fear extinction.

Effects of Western Diet on Cognition in Rodents

The diet eaten by many people in Australia and other developed countries is rich in saturated fat and refined carbohydrates. It has been known for some time that excessive intake of this so-called western diet leads to increases in body weight, even obesity, and a range of adverse health effects.

More recent evidence has linked this die with cognitive deficits across the lifespan. Laboratory rats, like people, avidly consume this diet, become overweight and develop a range of adverse health effects. They also exhibit cognitive deficits, particularly in tasks that require the hippocampus and surrounding cortices. Moreover, these deficits occur rapidly well in advance of increases in body weight and associated changes in health. 

The project uses laboratory rodents to study the effects of a western style diet on cognition. It has three aims. The first is to examine whether the cognitive deficits induced by short or long exposures to the diet are correlated with changes in neuroinflammatory and neurogenic markers in the hippocampus and in gut microbiota responses. The second is to asses ways of preventing or reversing the cognitive deficits, while the final aim is to determine the contributions of dat versus sugar to the cognitive deficits and associated molecular changes.  

Danger Changes the Way the Brain Processes Innocuous Information

The project uses sensory preconditioning as a tool to understand how the brain processes basic information, and how motivational states (such as fear) alter how the brain processes this type of information.

In sensory preconditioning, rodents first learn that an innocuous light signals an equally innocuous noise. They then learn that the noise is dangerous. The consequence of the noise becoming dangerous is that rodents are frightened when tested with the light. In a familiar environment, encoding of the light-noise association requires neuronal activity in the cortex but not the amygdala, whereas in a dangerous environment, encoding of the light-noise association requires activity in the amygdala but not in the cortex. Danger thus shifts processing of the light-sound association from the cortex to the amygdala.

Current work examines whether the experience of danger after encoding of the light-sound association shifts consolidation of the association from the cortex to the amygdala and whether other motivational states (e.g., hunger) also shifts processing of the association from the cortex to the amygdala.

Learning to Inhibit Fear

Clinical trials have established that cognitive behavioural therapy is relatively effective for disorders such as post-traumatic stress. A component of this therapy is cue exposure in which the patient, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. One aim of such confrontations is to reduce, even eliminate, the ability of these cues to elicit the fear and associated avoidance that impair the quality of the patient’s life. Extinction of learned fear responses in rodents is a laboratory model of cue exposure. The project uses rodents to study the psychological processes and neural mechanisms underlying extinction of learned fear.


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Address

School of Psychology
Mathews Building F23
UNSW Sydney NSW 2052
AUSTRALIA

Contact

Dr Nathan Holmes
n.holmes@unsw.edu.au
+612 9385 3523

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