Long-Term Potentiation at CA3-CA1 Hippocampal Synapses with Special Emphasis on Aging, Disease, and Stress

Abstract

Synaptic plasticity in the mammalian central nervous system has been the subject of intense investigation for the past four decades. Long-term potentiation (LTP), a major reflection of synaptic plasticity, is an activity-driven long-lasting increase in the efficacy of excitatory synaptic transmission following the delivery of a brief, high-frequency train of electrical stimulation. LTP is regarded as a principal candidate for the cellular mechanisms involved in learning and offers an attractive hypothesis of how memories are constructed. There are a number of exceptional full-length reviews published on LTP; the current review intends to present an overview of the research findings regarding hippocampal LTP with special emphasis on aging, diseases, and psychological insults.

Keywords: Alzheimer's disease; LTP; aging; brain; hippocampus; stress.

Figure 1

Schematic depiction of standard theta burst stimulation and primed-burst stimulation. (A) TBS consists of three trains of stimuli delivered 20 s apart. Each train is composed of 10 stimulus epochs delivered at 5 Hz (200 ms apart) with each epoch consisting of four pulses at 100 Hz. (B) PBS consists of a single priming pulse followed 170–200 ms later by a burst of stimuli delivered at 100–200 Hz (200 ms apart).

Figure 2

Multiple episodes of theta burst stimulation (TBS) induced maximal LTP, which is of similar amplitude in young adult and aged rats. Illustration of individual excitatory postsynaptic potentials from aged (gray circle) and young adult (open circle) rats before (10 min) and after (60 min) the last episode of TBS. Bar diagram represents mean percentage change in the slope of synaptic responses during the last 10 min of recording, 60 min following the sixth TBS episode (adapted from Kumar et al., 2007).

Figure 3

Pharmacological inhibition of intracellular Ca²⁺ stores by cyclopiazonic acid (CPA; 3 μM) led to LTP induction by a low-frequency (5 Hz, 900 pulses) stimulation protocol. Illustrations of the time course of mean percentage change in the synaptic responses during 10 min before and 60 min after delivery of 5 Hz stimulation (5 Hz/3 min, solid horizontal line) to the control and test path. LTP is observed only in test path (adapted from Kumar and Foster, 2004).

Figure 4

Enhance AHP amplitude during aging contributes to impaired LTP induction. (A) Representative intracellular current clamp recordings from a CA1 hippocampal pyramidal neuron in aged rat are shown after a train of five action potentials elicited by a 100-ms pulse of depolarizing current under conditions of CPA (3 μM) and following bath application of Bay K8644 (1 μM) in the presence of CPA. Note that under conditions of blockade of Ca²⁺ release from intracellular calcium stores by CPA, the L-channel agonist, Bay K8644 increased the AHP amplitude. (B) Time course of the synaptic responses following 5 Hz pattern stimulation in presence of Bay K8644 + CPA. LTP induced by 5 Hz stimulation was blocked under conditions of Bay K8644 + CPA in which AHP amplitude was increased (adapted from Kumar and Foster, 2004).