Keisuke Kawasaki

Inhibitory long-term potentiation underlies auditory conditioning of goldfish escape behaviour

Long-term potentiation (LTP), the increase in synaptic strength evoked by high-frequency stimulation, is often considered to be a cellular model for learning and memory. The validity of this model depends on the assumptions that physiological stimuli can induce LTP in vivo and that the resulting synaptic modifications correlate with behavioural changes. However, modifiable synapses are generally embedded deep in complex circuits. In contrast, the goldfish Mauthner (M)-cell and its afferent synapses are easily accessible for electrophysiological studies, and firing of this neuron is sufficient to trigger fast escape behaviour in response to sudden stimuli,. We have previously shown that tetanic stimulation can induce LTP of the feedforward inhibitory synapses that control the excitability of the M-cell,. Here we report that natural sensory stimulation can induce potentiation of this inhibitory connection that resembles the LTP induced by afferent tetanization. Furthermore, comparable acoustic stimulation produced a parallel decrease in the probability of the sound-evoked escape reflex. Thus we demonstrate for the first time, to our knowledge, a behavioural role for the long-term synaptic strengthening of inhibitory synapses.

Effects of Familiarity on Neural Activity in Monkey Inferior Temporal Lobe

Long-term familiarity facilitates recognition of visual stimuli. To better understand the neural basis for this effect, we measured the local field potential (LFP) and multiunit spiking activity (MUA) from the inferior temporal (IT) lobe of behaving monkeys in response to novel and familiar images. In general, familiar images evoked larger amplitude LFPs whereas MUA responses were greater for novel images. Familiarity effects were attenuated by image rotations in the picture plane of 45 degrees. Decreasing image contrast led to more pronounced decreases in LFP response magnitude for novel, compared with familiar images, and resulted in more selective MUA response profiles for familiar images. The shape of individual LFP traces could be used for stimulus classification, and classification performance was better for the familiar image category. Recording the visual and auditory evoked LFP at multiple depths showed significant alterations in LFP morphology with distance changes of 2 mm. In summary, IT cortex shows local processing differences for familiar and novel images at a time scale and in a manner consistent with the observed behavioral advantage for classifying familiar images and rapidly detecting novel stimuli.

Learning to Recognize Visual Objects With Microstimulation in Inferior Temporal Cortex

The malleability of object representations by experience is essential for adaptive behavior. It has been hypothesized that neurons in inferior temporal cortex (IT) in monkeys are pivotal in visual association learning, evidenced by experiments revealing changes in neural selectivity following visual learning, as well as by lesion studies, wherein functional inactivation of IT impairs learning. A critical question remaining to be answered is whether IT neuronal activity is sufficient for learning. To address this question directly, we conducted experiments combining visual classification learning with microstimulation in IT. We assessed the effects of IT microstimulation during learning in cases where the stimulation was exclusively informative, conditionally informative, and informative but not necessary for the classification task. The results show that localized microstimulation in IT can be used to establish visual classification learning, and the same stimulation applied during learning can predictably bias judgments on subsequent recognition. The effect of induced activity can be explained neither by direct stimulation-motor association nor by simple detection of cortical stimulation. We also found that the learning effects are specific to IT stimulation as they are not observed by microstimulation in an adjacent auditory area. Our results add the evidence that the differential activity in IT during visual association learning is sufficient for establishing new associations. The results suggest that experimentally manipulated activity patterns within IT can be effectively combined with ongoing visually induced activity during the formation of new associations.

Effect of glutamine on lymphoplasmacytic lymphoma, especially on the viewpoint of the differentiation into vulnerable subpopulation

Glutamine (Gln) is important not only for cell proliferation but also for differentiation. Although Gln is essential for plasmacytic differentiation of lymphocytes, no study has been done on the effect of Gln on differentiation of tumor cells, such as lymphoma. Here we examined the effect of Gln on plasmacytic differentiation of lymphoplasmacytic lymphoma (LPL) with its cell lines, MWCL-1 and RPCI-WM1. Gln promoted plasmacytic differentiation of LPL, and p38 MAPK signaling pathway mediated such differentiation. We previously reported that the subpopulation with plasmacytic differentiation was vulnerable to apoptosis in LPL. Although it is difficult to lead these findings to the radical therapy, they might help the treatment of LPL, in which stimulation of p38 MAPK by Gln induced differentiation of LPL into vulnerable subpopulation.

2320 Inhibitory long-term potentiation underlying long-lasting habituation of goldfish escape response

Previously we reported that activity of tonically active neurons (TANS) in the primate striatum which is conditionally related to sensory events used in behavioral tasks is acquired through the behavioral learning. Aim of this study was to identify structures supplying the conditioning input to the TANS. In a monkey (Macaca fuscata), click sound of solenoid valve was followed by a delivery of liquid reward. About 60% (74112 1) of TANS in the putamen and caudate nucleus became responsive to the click through 3 to 4 weeks of conditioning. In the thalamus ipsilateral to the striate recording, neurons were found to respond to the conditioning stimuli spec&cally in the centromedian and parafascicular nuclei. Then, we injected GABAA receptor agonist muscimol(38.l/15min.) to inactivate these structures. Most of TANS became non-responsive to the conditioning stimuli (8149 cells) after the muscimol injection. These results suggested that intralaminar nucleus of the thalamus supply sensory event-related information to the striatum, and that the TANS acquire conditioned responses to the sensory events through behavioral learning which includes involvement ofnigrostriatal dopamine system.

2319 Long-lasting habituation of mauthner cell-initiated escape response of goldfish

Previously we reported that activity of tonically active neurons (TANS) in the primate striatum which is conditionally related to sensory events used in behavioral tasks is acquired through the behavioral learning. Aim of this study was to identify structures supplying the conditioning input to the TANS. In a monkey (Macaca fuscata), click sound of solenoid valve was followed by a delivery of liquid reward. About 60% (74112 1) of TANS in the putamen and caudate nucleus became responsive to the click through 3 to 4 weeks of conditioning. In the thalamus ipsilateral to the striate recording, neurons were found to respond to the conditioning stimuli spec&cally in the centromedian and parafascicular nuclei. Then, we injected GABAA receptor agonist muscimol(38.l/15min.) to inactivate these structures. Most of TANS became non-responsive to the conditioning stimuli (8149 cells) after the muscimol injection. These results suggested that intralaminar nucleus of the thalamus supply sensory event-related information to the striatum, and that the TANS acquire conditioned responses to the sensory events through behavioral learning which includes involvement ofnigrostriatal dopamine system.