The effects of stress (restraint plus tail shock) on hippocampus-dependent trace eyeblink conditioning and hippocampal excitability were examined in C57BL/6 male mice. The results indicate that the stressor significantly increased the concentration of circulating corticosterone, the amount and rate of learning relative to nonstressed conditioned mice, and the excitability of CA1 hippocampal pyramidal neurons. Behaviorally, there was no effect of the stressor on control mice that received unpaired presentations of the tone and periorbital shock, i.e., neither stressed nor nonstressed control mice showed an increase in conditioned responding that was above baseline levels. Biophysically, the stressor significantly decreased the amplitude of the post-burst afterhyperpolarization (AHP) and decreased spike frequency accommodation relative to cells from nonstressed control mice. The effect was significant for mice that were stressed either 1 h or 24 h earlier. The results suggest that the stressor increases the excitability of hippocampal pyramidal neurons and that the mechanism underlying this increase may contribute to the more rapid acquisition of hippocampally dependent eyeblink conditioning.The hippocampus is critically important for the formation of memories, as observed in human patients with temporal lobe damage (Scoville and Milner 1957;Daum et al. 1993;Zola and Squire 2001) and as demonstrated by lesion studies in several species, including rabbits (Solomon et al. 1986;Moyer Jr. et al. 1990), rats (Weiss et al. 1999a) and mice (Takehara et al. 2002;Tseng et al. 2004). Electrophysiological studies using both extracellular single neuron recordings (Berger et al. 1983;Weiss et al. 1996;McEchron and Disterhoft 1997) and intracellular recordings of the biophysical properties of hippocampal pyramidal neurons (Disterhoft et al. 1986;Moyer Jr. et al. 1996) have also revealed learning and memory-specific changes in the firing patterns and biophysical properties of these neurons. These neurons are particularly responsive to behaviorally salient stimuli, especially those that help inform the animal of where it is in space (Wilson and McNaughton 1993) and those that predict the temporal occurrence of another stimulus (Berger et al. 1976).This innate responsiveness is also sensitive to adverse environmental conditions or stressors, which can either facilitate or inhibit the formation of new memories (Kim and Yoon 1998;de Kloet et al. 1999). The relationship between facilitation and inhibition for a particular stressor is likely due to the stimulus intensity in terms of magnitude, frequency, or duration (Shors and Servatius 1997), as well its timing relative to another event (Shors 2001). This relationship is often referred to as having an inverted U function; i.e., some stress facilitates behavior, but too much stress is detrimental. A better understanding of the relation which governs the effects of stress and behavior will be beneficial for understanding the neurobiological basis for stress-related disorders (Brewin 20...