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Transcript
The prefrontal cortex (PFC) is responsible for higher-level cognition, such as personality
expression and social behavior. The PFC has connections with the amygdala, locus coeruleus,
ventral tegmental area, and hippocampus. The PFC, however, is particularly susceptible to stress.
This research seeks to examine the effects of repeated stress on the plasticity, morphology and
membrane properties of PFC pyramidal neurons. These properties were examined in early
adolescent (P.38-42), mid adolescent (P.45-50) and adult (P 70-78) male and female SpragueDawley rats. The resident intruder paradigm was used as a social stress model (Koolhaas et al
2013). The Golgi impregnation method was used to visualize morphology.
Layer V pyramidal cells of the PFC were reconstructed analyzed using Neurolucida (MBF
Bioscience inc, Williston, VT). Currently, the adult male group has been completed. Evidently,
stressed rats had increased apical and basal dendrite length and reduced axon length. The number
of nodes and branches were not significantly different. Sholl analysis and complexity
measurements revealed increased complexity of apical and basal dendrites following stress.
Apical dendrite surface was significantly larger and basal dendrite volume was significantly
lower in stressed rats.
Prior studies have suggested that other forms of chronic stress, such as restraint stress
lead to dendritic atrophy. Following three weeks of repeated restraint stress, rats of the same age
and breed exhibited a 20% decrease in total apical dendritic length of layer II/III pyramidal
neurons (Radley et al. 2004). This present study suggests that social stress may cause different
neurochemical changes in contrast to other forms of chronic stress. It has been previously shown
that repeated social stress increases corticotropin releasing factor (CRF) release on the Locus
Coeruleus, resulting in increased norepinephrine (NE) release on the PFC (Van Bockstaele EJ,
Valentino RJ (2013). This finding suggests that morphological changes may arise from a NE
dependent mechanism. In the case that neurochemical changes are identical to those induced
from restraint stress and isolation stress, it would imply that layer V pyramidal cells respond
differently to chronic stress than those of layer II/III. These changes can impact cognition. For
example, layer II/III pyramidal neurons provide excitatory input to layer V pyramidal neurons
(Thomson and Bannister 2003), which plays a major part in goal-directed behaviors (Fuster
1991; Goldman-Rakic 1995). Therefore, morphological changes following social stress may alter
goal-oriented behavior. These changes also result in heightened brain reserves, which may
convey resilience to disease. For example, basilar dendrites of layer V pyramidal cells in
schizophrenia subjects had 40% fewer intersections in Sholl analysis, suggesting an association
between the disease and reduced dendritic complexity (Black 2004).
References
Black, James E., et al. "Pathology of layer V pyramidal neurons in the prefrontal cortex
of patients with schizophrenia." Pathology 161.4 (2004).
Fuster JM. The prefrontal cortex and its relation to behavior. Prog Brain Res 87: 201–
211, 1991.
Goldman-Rakic PS. Architecture of the prefrontal cortex and the central executive. Ann
NY Acad Sci 769: 71–83, 1995.
Koolhaas, J.M., Coppens, C.M., de Boer, S.F., Buwalda, B., Meerlo, P., Timmermans,
P.J.A. The Resident-intruder Paradigm: A Standardized Test for Aggression, Violence and
Social Stress. J. Vis. Exp. (77), e4367, doi:10.3791/4367 (2013)
Radley, J.J., Sisti, H.M., Hao, J., Rocher, A.B., McCall, T., Hof, P.R., McEwen, B.S.,
Morrison, J.H., 2004. Chronic behavioral stress induces apical dendritic reorganization in
pyramidal neurons of the medial prefrontal cortex. Neuroscience 125, 1–6. Radley, J.J., Rocher,
A.B., Janssen, W.G.M., H
Silvia-Gomez, A.B., Rojas, D., Juarez, I., Flores, G., 2003. Decreased dendritic spine
density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social
isolation rats. Brain Res. 983, 128–136.
Thomson AM and Bannister AP. Interlaminar connections in the neocortex. Cereb Cortex
13: 5–14, 2003
Van Bockstaele EJ, Valentino RJ (2013) Neuropeptide regulation of the locus coeruleus
and opiate-induced plasticity of stress responses. Adv Pharmacol 68:405-420.