Saori Nishijima

Appetitive Olfactory Learning and Long-Term Associative Memory in Caenorhabditis elegans

Because of the relative simplicity of its nervous system, Caenorhabditis elegans is a useful model organism to study learning and memory at cellular and molecular levels. For appetitive conditioning in C. elegans, food has exclusively been used as an unconditioned stimulus (US). It may be difficult to analyze neuronal circuits for associative memory since food is a multimodal combination of olfactory, gustatory, and mechanical stimuli. Here, we report classical appetitive conditioning and associative memory in C. elegans, using 1-nonanol as a conditioned stimulus (CS), and potassium chloride (KCl) as a US. Before conditioning, C. elegans innately avoided 1-nonanol, an aversive olfactory stimulus, and was attracted by KCl, an appetitive gustatory stimulus, on assay agar plates. Both massed training without an intertrial interval (ITI) and spaced training with a 10-min ITI induced significant levels of memory of association regarding the two chemicals. Memory induced by massed training decayed within 6 h, while that induced by spaced training was retained for more than 6 h. Animals treated with inhibitors of transcription or translation formed the memory induced by spaced training less efficiently than untreated animals, whereas the memory induced by massed training was not significantly affected by such treatments. By definition, therefore, memories induced by massed training and spaced training are classified as short-term memory (STM) and long-term memory (LTM), respectively. When animals conditioned by spaced training were exposed to 1-nonanol alone, their learning index was lower than that of untreated animals, suggesting that extinction learning occurs in C. elegans. In support of these results, C. elegans mutants defective in nmr-1, encoding an NMDA receptor subunit, formed both STM and LTM less efficiently than wild-type animals, while mutations in crh-1, encoding a ubiquitous transcription factor CREB required for memory consolidation, affected LTM, but not STM. The paradigm established in the present study should allow us to elucidate neuronal circuit plasticity for appetitive learning and memory in C. elegans.

Long-term appetitive memory in the nematode C. elegans

P1-m04 Sema4D/CD100 deficiency leads to superior performance in mouse motor behavior Takuji Ito 1 , Tetsuji Tanaka 2, Kenji Yoshida 1, Noriko Takeuchi 1, Hitoshi Kikutani 3, Atsushi Kumanogoh 4, Kazunori Yukawa 1 1 Dept Physiol, Fac of Pharm, Meijo Univ, Nagoya 2 Dep. of Obstetrics & Gynecology, Wakayama Med. Univ 3 Dep. of Molecular Immunology, Research Institute for Microbial Diseases, Osaka Univ 4 Dep. of Immunopathology, Research Institute for Microbial Diseases, Osaka Univ

Acute painful neuropathy of the perineum and scrotum following rapid improvement of glycemic control in type 1 diabetes

Post-treatment painful neuropathy (PPN) is sometimes caused by initiation of insulin treatment or strict glycemic control in patients with diabetes mellitus. A 28-year-old man, having type 1 diabetes mellitus for 5 years, was admitted to hospital with pain of the perineum and scrotum in December 2007. The pain was sharp, tingling, and burning in character, and was precipitated by contact with blankets or clothes. Sensory examination indicated that he had allodynia when pressure with a hand or pin was applied to the skin at the level of sacral 1–3 without sensory deficit. On neurological examination, the knee jerk reflex, Achilles tendon reflex, motor nerve conduction velocity (in the ulnar and peroneal nerves) and sensory nerve conduction velocity (in the ulnar and sural nerves) were normal. Laboratory tests showed a high glucose level of 220 mg/dL and a hemoglobin A1C (HbA1C) of 9.3%. There was no evidence of nephropathy and retinopathy. The patient had been hospitalized with ketoacidosis for 4 weeks in the department of internal medicine 3 months previously. The HbA1C levels at the time of previous admission and discharge were 17.4% and 13.5%, respectively. After discharge from hospital, the man adopted a healthier lifestyle that included using insulin as scheduled, following a strict diet, and ceasing to drink alcohol. The patient’s neuropathy was attributed to the previous rapid improvement of hyperglycemia, as indicated by the marked decrease of HbA1C. While a low dose of gabapentin (300 mg/ day) along with imipramine hydrochloride and mexitiline had no effect on his severe pain, a high dose of gabapentin (2000 mg/day) decreased his pain from 10/10 to 3/10 on a visual analog scale (VAS). When the gabapentin dose was decreased to 900 mg/day, his pain returned to 10/10 on the VAS. He was therefore maintained on a high dose of gabapentin (1600 mg/day). After discharge from hospital, his symptoms gradually improved, and drug therapy was discontinued at the end of September 2008 (Fig. 1). To make a diagnosis of PPN, it is important to distinguish it from diabetic painful polyneuropathy. Diabetic painful polyneuropathy is a long-term complication that results from poor glycemic control. PPN is also a secondary condition caused by strict glycemic control after long-term hyperglythemia. To distinguish PPN from diabetic painful polyneuropathy, it is important to keep the history of the previous glycemic control and the rapid improvement of hyperglycemia. Possible etiologies for PPN include nerve regeneration, metabolic abnormality, hemodynamic change in the endoneurium surrounding the nerve, or immunologic reaction to insulin. Gabapentin, a structural analog of g-amino butyric acid , appears to inhibit peripheral sensitization by blocking the activity of afferent C-fibers, while the central action of gabapentin within the spinal cord or brain reduces the sensitization of dorsal horn neurons. These combined peripheral and central actions of gabapentin might have been responsible for the alleviation of pain due to PPN in our patient. In order not to miss the diagnosis of PPN, it is important to keep the features of this condition in mind.