Studies on stress-induced modulation of long term potentiation in rodent hippocampus: what can we learn about pathogenesis of depression?

Abstract

Long-term potentiation (LTP) reflecting continuous changes in synaptic efficacy is regarded as a cellular model of learning and memory. In this mini-review the data relating to hippocampal LTP alterations in rodent models of depression are analyzed to learn whether disturbances in LTP may be reliable markers of synaptic plasticity impairments underlying depressive and anxiety states. LTP disturbances result from synaptic reorganizations induced by multiple inter-related and mutually dependent events: hypothalamic-pituitary-adrenal axis disfunction; malfunction of neurotransmitter systems; failure to maintain the balance of neurotrophic systems; neuroinflammatory processes; disturbance in neurogenesis. Stable deficits in hippocampal LTP reflect the synapse-related basic mechanisms for cognitive and emotional behavioral deficits characterisic for depression/anxiety, and altered LTP is indicative of the development of stress-induced psychopathology.Correspondence to: Natalia V.Gulyaeva, Institute of Higher Nervous Activity and Neurophysiology RAS, 5a Butlerov Street, Moscow, 117485, Russia, E-mail: nata_gul@pisem.net Key words: depression, anxiety, synaptic plasticity, long term potentiation (LTP), stress LiteratureChronic stress is considered to be a major risk factor in the development of mood diseases. In order to study mechanisms involved in the etiology of human affective disorders, there is an abundant use of various animal models based on different stress paradigms. Depressive disorders are the most common psychiatric pathology, and a great number of people who experience depression also experience anxiety. Sometimes, anxiety is more expressed than depression, while in many cases neither is clearly predominant. In rodent stress-based models anxiety and depression symptoms often are demonstrated in parallel.Activity-dependent changes in synaptic strength are widely accepted as key mechanisms for information storage in the brain [1]. Long-term potentiation (LTP) is an electrophysiological phenomenon, an hours-lasting increase of postsynaptic potentials after tetanization. It is believed to reflect long-term changes in synaptic efficacy in distributed networks, associated with constant changes in the behavioral phenomena, which are often interpreted as the retention of information [2]. Thus, hippocampal LTP is regarded as a cellular model of learning and memory. Cognitive impairments and LTP impairments are increasingly recognized as events accompanying and reflecting experimental depression, anxiety and other experimental stress-related chronic psychological disorders, therefore, disturbances in LTP may be reliable markers of synaptic plasticity impairments underlying depressive and anxiety states. The dentate gyrus (DG) of the hippocampus is supposed to play a critical role in defining the impact of stress on hippocampal functioning. The DG is a dynamic structure susceptible to stress, its variable and complex stress response being reflected in changes of LTP and local circuit activity associated wit...

Modulations on Neurogenesis Due to Chronic Unpredictable Stress in Adult Male Albino Rats: Overactivation of Neural Stem Cells and Microglia

“…Also, this result was compatible with [21,22] who explained the memory impairment recorded in behavioral tests to impairment in long term potentiation in place cells of CA1 owing to a decrease in brain-derived neurotrophic factor and cyclic adenosine triphosphate (cAMP) response element protein, which regulates long term potentiation. This memory impairment in chronically stressed rats may be attributed to dysfunction in hypothalamic-pituitaryadrenal axis, imbalance of neurotrophic factors, and decrease in AMPA receptors, mainly in temporoammonic synapses of CA1, which is essential in memory consolidation [23] . Thus, the chronic unpredictable stress initiated variable degenerative pathways leading to impairment in memory formation.…”