Kayoko Uezu

Septo-hippocampal drug interactions in post-trial memory processing.

To determine if serotonin and GABA regulate post-trial memory processing of the cholinergic projection from the septum to the hippocampus, mice were trained on footshock avoidance in a T-maze. Immediately after training, drugs were injected into the septum, hippocampus or both. Retention was tested 1 week after training and drug administration. Ketanserin, a serotonin type 2 receptor antagonist at a dose of 0.5 ng, had no measurable effect on retention, but it reduced the dose of bicuculline, in the septum, or arecoline in the hippocampus that was needed to improve retention. DOI, a serotonin type 2 receptor agonist at a dose of 2.5 ng, had the opposite effect of increasing the doses of bicuculline and arecoline needed to improve retention. Bicuculline, a GABA(A) receptor antagonist at a dose of 0.1 pg, did not affect retention when injected alone into the septum, but it reduced the dose of arecoline needed to improve retention in the hippocampus. Muscimol, a GABA(A) receptor agonist at a dose of 5 ng, injected into the septum, increased the dose of arecoline needed to improve retention. The results of this study are compatible with models that propose that serotonin innervation from the median raphe drives GABA interneurons in the medial septum that synapse on cholinergic neurons projecting to the hippocampus.

The pharmacology of post-trial memory processing in septum

The septum is recognized as important in learning and memory, but relatively little is known about the role of specific neurotransmitter receptors in memory processing in the septum. We evaluated the role of the classical neurotransmitters in mice that were prepared for intraseptal microinfusion of drug solution after footshock avoidance training in T-maze. Retention for the footshock training was determined 1 week after training and drug administration. The results indicated that receptor agonists of dopamine, norepinephrine, glutamate and acetylcholine improved retention, while the antagonists impaired retention. Receptor agonists of serotonin, gamma-amino butyric acid (GABA) and opioids impaired retention, while antagonists improved retention.

Lack of nociceptin receptor alters body temperature during resting period in mice.

The role of nociceptin (NOC) receptor on body core temperature (Tcore) control was examined using NOC receptor knockout mice. In homozygote NOC receptor-knockout, wild-type, and control C57BL/6J and 129/SV mice, Tcore was continuously recorded under 12:12 h light:dark (LD) and conditions of constant darkness (DD). The Tcore values during the resting period were higher in the NOC receptor-knockout mice than in both wild-type and control mice under both LD and DD conditions. Spontaneous activity during the resting period and plasma cortisol levels were not different between the NOC receptor-knockout and control mice. The findings herein indicate that the NOC receptor is involved in the control of Tcore during the resting period and is independent of light, physical activity and/or cortisol regulation.

Enhanced hippocampal acetylcholine release in nociceptin-receptor knockout mice

Nociceptin (NOC), an endogenous ligand of the opioid receptor-like 1 receptor, is thought to be involved in learning and memory processes. Since acetylcholine (ACh) is involved in hippocampal function, and the hippocampus plays a critical role on the learning and memory function, hippocampal ACh release in NOC-receptor knockout mice was examined using an in vivo microdialysis method. The release of hippocampal ACh was largely increased in the knockout mice. Furthermore, in the knockout mice, an enhanced hippocampal theta rhythm, which is known to be linked to hippocampal memory function, was also observed. Immunohistochemically, in septum, co-existence of NOC receptor with cholinergic, but not with GABAergic neurons, was verified. The findings demonstrate that the NOC receptor is involved in hippocampal cholinergic function.

Age-related changes in hippocampal theta rhythm in SAMP8 mouse

Abstract It is well known that the hippocampal theta wave is highly correlated with cognitive functions such as attention, memory and learning. Moreover, a number of studies suggest that hippocampal theta power is cholinergically mediated. In the present study, we examined age-related changes in hippocampal theta rhythm before and after T-maze footshock avoidance learning in 4- and 12-month-old SAMP8 mice using fast Fourier transformation of a hippocampal electroencephalogram. The peak power was significantly lower in 12- than in 4-month-old SAMP8 mice. The peak frequency remained unchanged in both age groups. More trials were required to reach the criterion in T-maze learning in 12- than in 4-month-old SAMP8 mice. These results suggest a possible age-related dysfunction of the septohippocampal cholinergic system in 12-month-old SAMP8 mice.