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Stress-induced Modulation of Cells in the Amygdala and Hippocampus

von Mallissa Watts

Mallissa Watts, a student of the Elite Graduate Program Neuro-Cognitive Psychology, performed her second research project at the University of Washington to investigate the relationship between place cell remapping and activity of fear encoding neurons in the amygdala.

Emotions have evolved to serve a functional role in the survival of organisms. A key example, are the emotions of fear and stress which instantly provoke an animal to flee from danger thus directly enhancing survival. However, prolonged and high levels of stress have been shown to have serious adverse effects such as higher risk of diabetes, hypertension, immunosuppression, reproductive impairments, and neuronal cell death (McEwen and Sapolsky, 1995; Kim and Yoon, 1998).

The hippocampus, a critical brain structure for memory, spatial navigation and learning, is one of the brain areas most affected by stress due to its high levels of glucocorticoid receptors and involvement in inhibiting the stress response via the hypothalamus-pituitary-adrenal axis (Reul & de Kloet, 1985; McEwen & Sapolsky, 1995). A unique hippocampal cell that underlies crucial cognitive processes like spatial memory are known as place cells (O'Keefe & Dostrovsky, 1971). Place cells fire preferentially at specific locations in a known environment, conjunctively forming a cognitive map of external space. In a novel environment, place cells begin to form preferred 'place fields' - locations at which a specific place cell fires maximally. Within a number of minutes the 'place field' of each place cell becomes stable and remains stable in future visits to the same environment. Interestingly, stress has a direct impact on hippocampal place cells by interfering with the stability of place cell maps. While stress-induced behavioral and cognitive impairments have been strongly evidenced, the link between the emotion of stress and impaired memory and place map stability remains unclear. Recently, considerable evidence has pointed to the amygdala, a brain region which projects to several areas of the hippocampus including CA1, as a critical modulator of stress on hippocampal functioning (Kim et al., 2001, Vouimba & Richter-Levin, 2005, Choi & Kim, 2010).

In the current study we explored the relationship between hippocampal spatial representation and the amygdala-fear response to determine whether  place cell remapping correlates to activity of fear encoding neurons in the amygdala. To do this we recorded cells in the hippocampus and amygdala of rats foraging for food in a semi-naturalistic environment. After training, rats encountered a 'predator' (remote-controlled robot) which induced fear behavior in all rats. Animals were given 10 foraging attempts per session. Place cells were classified into three types based on whether they fired maximally inside the nest, near the nest or distant from the nest (Figure 1). Amygdala recordings were assessed in three sessions: before the presence of the predator, during predator presence and after predator presence. While analysis was limited by the brief research project time course, raster charts indicated a change in amygdala cell firing rates between the three sessions (Figure 2). Full analysis is currently ongoing.

The link between the amygdala and hippocampus in high-stress conditions is not yet fully understood. One pertinent question that remains unanswered is the evolutionary functionality of impaired memory after stress. An interesting proposal for the evolutionarily advantageous role of stress and impaired memory is that impaired memory following stress may serve a psychologically beneficial role to dilute the strength of traumatic memories (Kim et al., 2005) This hypothesis can serve to explain stress disorders like PTSD, indicating that a failure of the system to efficiently dilute traumatic memories may heighten psychological distress and impair evolutionarily beneficial behaviors. The advances in understanding the underlying neurobiological link between stress and impaired behavior have been striking in the past decades, from revealing that the direct impairment of the hippocampus by stressors to illustrating the critical role of the amygdala in regulating hippocampal involvement. However, much research has yet to be done. A deeper understanding of these underlying mechanisms has the potential to provide more accurate and beneficial guidance for the treatment of anxiety and stress disorders.

Mi-Seon Kong, Dr. Jeansok Kim
Department of Psychology and Neurobiology & Behavior, University of Washington, Seattle, USA

Dr. George Boyan
Faculty of Biology – Neurobiology, Ludwig Maximilians University Munich, Germany

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