Neuronal major histocompatibility complex class I molecules are implicated in the generation of asymmetries in hippocampal circuitry.

Left-right asymmetry is a fundamental feature of higher-order brain function; however, the molecular basis of brain asymmetry has remained unclear. We have recently demonstrated asymmetries in hippocampal circuitry resulting from the asymmetrical allocation of NMDA receptor (NMDAR) subunit GluR2 (NR2B) in pyramidal cell synapses. This asymmetrical allocation of 2 subunits affects the properties of NMDARs and generates two populations of synapses, '2-dominant' and '2-non-dominant' synapses, according to the hemispheric origin of presynaptic inputs and cell polarity of the postsynaptic neurone. To identify key regulators for generating asymmetries, we analysed the hippocampus of ß2-microglobulin (ß2m)-deficient mice lacking cell surface expression of major histocompatibility complex class I (MHCI). Although MHCI proteins are well known in the immune system, accumulating evidence indicates that MHCI proteins are expressed in the brain and are required for activity-dependent refinement of neuronal connections and normal synaptic plasticity. We found that ß2m proteins were localised in hippocampal synapses in wild-type mice. NMDA EPSCs in ß2m-deficient hippocampal synapses receiving inputs from both hemispheres showed similar sensitivity to Ro 25-6981, an 2 subunit-selective antagonist, with those in '2-dominant' synapses for both the apical and basal synapses of pyramidal neurones. The structural features of the ß2m-deficient synapse in addition to the relationship between the stimulation frequency and synaptic plasticity were also comparable to those of '2-dominant' synapses. These observations indicate that the ß2m-deficient hippocampus lacks '2-non-dominant' synapses and circuit asymmetries. Our findings provide evidence supporting a critical role of MHCI molecules for generating asymmetries in hippocampal circuitry.

Activity changes in jaw motor neurons induced by egg-laying hormone contribute to the feeding suppression during egg-laying behavior in Aplysia kurodai.

Egg-laying behavior in Aplysia is accompanied by behavioral changes such as feeding suppression. We investigated the effects of the egg-laying hormone (ELH) on food intake, the activity patterns of jaw muscles, and the activity of buccal neurons (multi-action neuron [MA1] and jaw-closing motor neuron [JC2]), which are elements of the feeding neural circuits controlling jaw movements in Aplysia kurodai. Injection of ELH into the body cavity inhibited the intake of seaweed. After ELH application, the rhythmic activity of jaw muscles that was induced by preferred taste stimulation elicited fewer ingestion-like responses and increased the number of rejection-like responses. ELH applied to the buccal ganglia increased the firing activity of JC2 during spontaneous rhythmic responses and during the rhythmic feeding-like responses that were evoked by electrical stimulation of the esophageal nerves. In the 2 types of rhythmic responses, the Dn (normalized value of the delay time of JC2 firing onset) decreased after ELH application as compared with the control. Furthermore, ELH decreased the size of MA1-induced inhibitory postsynaptic currents in JC2. These results suggest that ELH changes the buccal motor program from ingestion to rejection on the basis of our previous results, and may contribute to a decrease in food intake during egg laying.

Effective amino acid composition of seaweeds inducing food preference behaviors in Aplysia kurodai.

Aplysia kurodai feeds on Ulva but rejects Gelidium and Pachydictyon with distinct patterned jaw movements. We previously demonstrated that these movements are induced by taste alone. Thus some chemicals may contribute to induction of these responses. We explored the amino acids composition of Ulva, Gelidium and Pachydictyon extracts used during our taste-induced physiological experiments. These solutions contained many constituents. The concentrations of six amino acids (Asp, Asn, Glu, Gln, Phe, Tau) were obviously different in the three extract solutions. We explored patterned jaw movements following application of solutions containing a pure amino acid. We statistically compared the occurrence numbers of ingestion-like and rejection-like patterned jaw movements (positive and negative values, respectively) for each amino acid. Our results suggested that L-Asn tends to induce ingestion-like responses, likely resulting in a preference of Ulva. In contrast, L-Asp tends to induce rejection-like responses, likely resulting in aversion towards Pachydictyon. In addition, we demonstrated that L-Asn and L-Asp solutions were sufficient to induce muscle activity associated with ingestion-like or rejection-like responses in the jaw muscles of a semi-intact preparation.

Alantrypinone and its derivatives: synthesis and antagonist activity toward insect GABA receptors.

The gamma-aminobutyric acid (GABA) receptor bears important sites of action for insecticides. Alantrypinone is an insecticidal alkaloid that acts as a selective antagonist for housefly (vs rat) GABA receptors, and is considered to be a lead compound for the development of a safer insecticide. In an attempt to obtain compounds with greater activity, a series of racemic alantrypinone derivatives were systematically synthesized using hetero Diels-Alder reactions, and a total of 34 compounds were examined for their ability to inhibit the specific binding of [(3)H]4'-ethynyl-4-n-propylbicycloorthobenzoate, a high-affinity non-competitive antagonist, to housefly-head membranes. The assay results showed that (1) there is no significant difference between the potencies of natural (+)-alantrypinone and its synthetic racemate; (2) the amide NHs at the 2- and 18-positions are important for high activity; (3) there is a considerable drop in potency for compounds without an aromatic ring at the 16-position; and (4) a large substituent at the 3-position is detrimental to high activity.

Responses of cerebral GABA-containing CBM neuron to taste stimulation with seaweed extracts in Aplysia kurodai.

Aplysia kurodai distributed along Japan feeds well on Ulva pertusa but rejects Gelidium amansii with distinctive patterned movements of the jaws and radula. On the ventral side of the cerebral M cluster, four cell bodies of higher order neurons that send axons to the buccal ganglia are distributed (CBM neurons). We have previously shown that the dopaminergic CBM1 modulates basic feeding circuits in the buccal ganglia for rejection by firing at higher frequency after application of the aversive taste of seaweed such as Gelidium amansii. In the present experiments immunohistochemical techniques showed that the CBM3 exhibited gamma-aminobutyric acid (GABA)-like immunoreactivity. The CBM3 may be equivalent to the CBI-3 involved in changing the motor programs from rejection to ingestion in Aplysia californica. The responses of the CBM3 to taste stimulation of the lips with seaweed extracts were investigated by the use of calcium imaging. The calcium-sensitive dye, Calcium Green-1, was iontophoretically introduced into a cell body of the CBM3 using a microelectrode. Application of Ulva pertusa or Gelidium amansii extract induced different changes in fluorescence in the CBM3 cell body, indicating that taste of Ulva pertusa initially induced longer-lasting continuous spike responses at slightly higher frequency compared with that of Gelidium amansii. Considering a role of the CBM3 in the pattern selection, these results suggest that elongation of the initial firing response may be a major factor for the CBM3 to switch the buccal motor programs from rejection to ingestion after application of different tastes of seaweeds in Aplysia kurodai.

Spike encoding of olfactory receptor cells.

Olfaction begins with the transduction of the information carried by odorants into electrical signals in olfactory receptor cells (ORCs). The binding of odor molecules to specific receptor proteins on the ciliary surface of ORCs induces the receptor potentials. This initial excitation causes a slow and graded depolarizing voltage change, which is encoded into a train of action potentials. Action potentials of ORCs are generated by voltage-gated Na+ currents and T-type Ca2+ currents in the somatic membrane. Isolated ORCs, which have lost their cilia during the dissociation procedure, are known to exhibit spike frequency accommodation by injecting the steady current. This raises the possibility that somatic ionic channels in ORCs may serve for odor adaptation at the level of spike encoding, although odor adaptation is mainly accomplished by the ciliary transduction machinery. This review discusses current knowledge concerning the mechanisms of spike generation in ORCs. It also reviews how neurotransmitters and hormones modulate ionic currents and action potentials in ORCs.

Cerebral CBM1 neuron contributes to synaptic modulation appearing during rejection of seaweed in Aplysia kurodai.

The Japanese species Aplysia kurodai feeds well on Ulva but rejects Gelidium with distinctive rhythmic patterned movements of the jaws and radula. We have previously shown that the patterned jaw movements during the rejection of Gelidium might be caused by long-lasting suppression of the monosynaptic transmission from the multiaction MA neurons to the jaw-closing (JC) motor neurons in the buccal ganglia and that the modulation might be directly produced by some cerebral neurons. In the present paper, we have identified a pair of catecholaminergic neurons (CBM1) in bilateral cerebral M clusters. The CBM1, probably equivalent to CBI-1 in A. californica, simultaneously produced monosynaptic excitatory postsynaptic potentials (EPSPs) in the MA and JC neurons. Firing of the CBM1 reduced the size of the inhibitory postsynaptic currents (IPSCs) in the JC neuron, evoked by the MA spikes, for >100 s. Moreover, the application of dopamine mimicked the CBM1 modulatory effects and pretreatment with a D1 antagonist, SCH23390, blocked the modulatory effects induced by dopamine. It could also largely block the modulatory effects induced by the CBM1 firing. These results suggest that the CBM1 may directly modulate the synaptic transmission by releasing dopamine. Moreover, we explored the CBM1 spike activity induced by taste stimulation of the animal lips with seaweed extracts by the use of calcium imaging. The calcium-sensitive dye, Calcium Green-1, was iontophoretically loaded into a cell body of the CBM1 using a microelectrode. Application of either Ulva or Gelidium extract to the lips increased the fluorescence intensity, but the Gelidium extract always induced a larger change in fluorescence compared with the Ulva extract, although the solution used induced the maximum spike responses of the CBM1 for each of the seaweed extracts. When the firing frequency of the CBM1 activity after taste stimulation was estimated, the Gelidium extract induced a spike activity of ~30 spikes/s while the Ulva extract induced an activity of ~20 spikes/s, consistent with the effective firing frequency (>25 spikes/s) for the synaptic modulation. These results suggest that the CBM1 may be one of the cerebral neurons contributing to the modulation of the basic feeding circuits for rejection induced by the taste of seaweeds such as Gelidium.