Responsiveness of the cortical taste area neurons to a mixture of the four basic tastants in rats.

The taste coding mechanism in the cortical taste area was investigated by analyzing the responses of 59 neurons in the cortical taste area of the anesthetized rat to a mixture of the four basic tastants in both absence and presence of bicuculline methiodide, a specific antagonist to the GABA(A) receptors. The mixture caused response suppression more frequently than response facilitation, both in the control state and during bicuculline application. Cluster analysis revealed that only a group of the neurons with the best response to both NaCl and HCl (group NH) showed the best response to the mixture in the control state, whereas during bicuculline application, in addition to group NH, two other groups of neurons responding to sucrose, or to HCl and quinine responded vigorously to the mixture. Multidimensional scaling located the mixture outside the space of the four basic tastants facing an NaCl-HCl line in both states. GABAergic inhibition caused the group NH to represent the taste of the mixture in the control state. Thus, the mixture probably tastes salty and sour to rats. No cortical neuron was found which specifically responded to the mixture.

GABAergic inhibition and modifications of taste responses in the cortical taste area in rats.

Using multibarrel electrodes, recordings were made in the cortical taste area (CTA), specifically in the granular and dysgranular parts of the insular cortex (areas GI and DI), of urethane-anesthetized rats. The effects of an iontophoretic application of gamma-aminobutylic acid (GABA) and bicuculline methiodide (BMI), a specific antagonist to the GABA(A) receptor, were tested. GABA decreased background discharges in ca. 69% of 509 neurons in both areas, and in ca. 58% of 64 taste neurons. BMI antagonized the inhibitory action of GABA in CTA neurons and facilitated background discharges in ca. 51% of the 390 neurons tested, including ca. 69% of the 52 taste neurons, which indicates that CTA neurons have GABA(A) receptors to receive inhibitory inputs from interneurons. In both areas, the effects of BMI (6-20 nA) on taste responses of the 85 CTA neurons (49 and 36 in areas GI and DI, respectively) to the four basic taste stimuli were examined: 65 neurons were recognized in the absence of BMI, whereas 20 only in the presence of the drug. BMI increased taste responses in 25 of the former group and changed the type of their response profiles in 25 including 12 neurons whose responses were increased. It also changed the best stimulus in 34 neurons. The drug affected the receptive fields in almost all cases examined (n = 23) and increased the size in 78.2% when the value for all four basic taste stimuli were totaled. New receptive fields were uncovered by BMI in varying regions of the oral cavity depending on the taste stimulus. But the drug decreased taste responses in several neurons (n = 8). These findings indicate that the GABAergic inhibitory system apparently contributes to modifying or selecting taste information in both areas of the CTA.

NMDA and non-NMDA receptors mediate taste afferent inputs to cortical taste neurons in rats.

Two main subclasses of ionotropic receptors for excitatory amino acids (EAAs), N-methyl-D-aspartate (NMDA) receptors and non-NMDA receptors, are involved in neurotransmission in the cortex of mammals. To examine whether EAAs are transmitters at the cortical taste area (CTA) in rats and to elucidate which types of the two ionotropic receptors operate at these synapses, we studied the effects of microiontophoretic administration of EAA antagonists on the responses of 64 taste cortical neurons to four basic taste stimuli in urethane-anesthetized rats. Both D-2-amino-5-phosphonovalerate (APV), a selective antagonist for NMDA receptors, and 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), a selective antagonist for non-NMDA receptors, suppressed most of the taste responses. The percentage of neurons suppressed by APV (70.3%) was almost the same as that suppressed by CNQX (64.1%). These suppressive effects were independent of the effects of background discharges during the prestimulus, water-rinsing period. The percentage of neurons suppressed by the antagonists did not differ between any pairs of taste stimuli. The number of neurons possessing both receptors was larger in the granular insular area (area GI), one of the two CTAs, than in the dysgranular insular area (area DI). In addition, taste responses were suppressed by CNQX or by both APV and CNQX in area GI in a significantly larger number of layer V neurons than in area DI. The present results indicate that normal excitatory transmission of taste afferents in the CTA in rats was mediated by both NMDA and non-NMDA receptors. The finding that a large fraction of neurons in the CTA in rats mediated taste information through NMDA receptors in normal transmission might be related to the higher potency of the plasticity observed in the CTA.

[Type IV collagenase activities in human colorectal cancers and its role in cancer invasion and metastasis].

In 36 patients with colorectal cancers, type IV collagenase activities were measured in cancer and non-cancer tissues for evaluating its role in the process of cancer invasion and metastasis. The colorectal cancer tissues revealed remarkably higher activities than the distant normal and tumor-neighboring mucosa (p < 0.001). The activities in the colorectal cancer tissues with high-grade histological venous invasion were higher than those with low-grade histological venous invasion (p < 0.005). But no differences of the activities were found between patients with and without hepatic metastasis. These results suggest that the type IV collagenase plays an important role in the cancer invasion to the blood vessels around the primary site in colorectal cancers.