TOP ＞ Symposia

Symposia Roles of monoamnes in adaptive behavior: regulation of mood and emotion／モノアミンによる気分・情動の調節と適応行動 1S5-1 Elucidating the role and functions of prefrontal dopaminergic signaling towards identifying a neuronal circuit underlying stress resilience Tomoyuki Furuyashiki Div Pharmacol, Grad Sch Med, Kobe Univ Stress from social and environmental stimuli induces emotional changes such as depression and elevated anxiety, and precipitates mental illnesses. Using repeated social defeat stress in mice, we previously reported that single stress induces dopaminergic response in the medial prefrontal cortex (mPFC), which suppresses the induction of social avoidance, whereas repeated stress attenuates this dopaminergic response, leading to social avoidance. However, the role and functions of prefrontal dopaminergic signaling for stress resilience was unknown. Here we knocked down the expression of dopamine receptor subtype in a specific type of mPFC neurons and found that dopamine D1 receptor subtype in mPFC excitatory neurons is critical for suppressing stress-induced social avoidance. Repeated stress induces dendritic atrophy of mPFC excitatory neurons in a manner correlated to the level of social avoidance, but D1 receptor subtype in mPFC is not involved in this dendritic atrophy. By contrast, single stress induces dendritic growth of mPFC excitatory neurons through D1 receptor signaling in these neurons. Therefore, stress can induce either an adaptive response to augment stress resilience through D1 receptor subtype in mPFC or a maladaptive response to induce emotional abnormalities mediated by another mechanism, and repeated stress causes the shift from the former to the latter. In this symposium, I will present our recent findings described above as well as our attempts to identify a neuronal circuit for stress resilience regulated by D1 receptor subtype in mPFC. 1S5-2 Regulatory mechanism of hypothalamic corticotropin-releasing factor neurons by the ascending monoaminergic systems Keiichi Itoi1，Kenji Sakimura2 1Lab Info Biol, Grad Sch Info Sci, Tohoku Univ，2Dept Cell Neurobiol, Brain Res Inst, Niigata Univ Corticotropin-releasing factor (CRF) plays a key role in the regulation of the hypothalamic-pituitary-adrenal axis, but CRF is also distributed broadly in the brain and may play roles as a neurotransmitter and/or modulator. However, there have been no detailed morphological descriptions of CRF neurons in the mouse brain. The major obstacle in identifying CRF neurons is the difficulty in staining CRF neurons by immunohistochemistry using anti-CRF antibodies. We examined the morphological features of CRF neurons in the CRF-VenusDeltaNeo mouse line in which modified yellow fluorescent protein (Venus) was expressed under the CRF promoter (Brain Struct Funct 2017). In the CRF-VenusDeltaNeo mouse brain, most Venus-expressing neurons co-express CRF mRNA. Venus-expressing neurons constitute a discrete population of neuroendocrine neurons in the paraventricular nucleus of the hypothalamus (PVH) that project to the median eminence. Venus-expressing neurons were also found in brain regions outside the neuroendocrine PVH. By patch-clamp recordings from Venus-expressing CRF neurons in the PVH, we found that CRF neurons in the PVH receive direct glutamatergic and GABAergic inputs. The frequency of excitatory postsynaptic current or inhibitory postsynaptic current was altered by bath application of noradrenaline or serotonin. These actions of monoamines were attenuated by selective antagonists to the respective transmitter. It was suggested, from the present results, that hypothalamic CRF neurons may be regulated by the ascending monoaminergic inputs to the hypothalamus via glutamatergic and/or GABAergic interneurons. Further studies are necessary for elucidating the physiological roles of the ascending monoaminergic systems in the regulation of the hypothalamic stress-coping system. 1S5-3 The role of dorsal raphe neurons for integration of reward information with emotional context. Kae Nakamura，Masaharu Yasuda Dept.Physiol. Kansai Medical Univ. Dopamine and serotonin are monoamine neurotransmitters essential for normal brain function. The dopamine system is implicated in encoding reward prediction error and salient stimuli. To elucidate further the function of serotonin system compared with dopamine, we analyzed single neurons’ activity of the dorsal raphe nucleus (DRN), a major source of serotonin, and compared it with the activity of the substantia nigra pars compacta, a major source of dopamine, while monkeys performed Pavlovian procedure with an appetitive context where a reward was available and an aversive one where an airpuff was delivered.We found that half of the recorded DRN neurons discriminated between appetitive and aversive contexts by tonic modulation in their activity. In the appetitive context, they then kept track of expected reward value indicated by the conditioned stimuli. In the aversive context, the same neurons maintained tonic modulation in their activity throughout the block. However, modulation of their responses to trial events depending on airpuff probability was less common. These results indicate that single DRN neurons encode both appetitive and aversive information, but over differing time scales: a tonic one to discriminate emotional contexts, and a phasic one to encode rewarding events. Such temporally distinct DRN neuronal activities may provide the neural basis of modulation of decision making process in different emotional contexts. Despite neurochemical variability, measurement of single DRN neurons’ activity in behaving monkeys would provide significant understandings of principles that govern their activity. 1S5-4 Reading out reinforcement leaning and decision-making processes from neuronal activity of PPTg Yasushi Kobayashi1,2 1Osaka University Graduate School of Frontier Biosciences，2Center for Information and Neural Networks The pedunculopontine tegmental nucleus (PPTg), consisting of cholinergic and non-cholinergic neurons, is involved in the regulation of motor control and cognitive processes. PPTg has many interconnections with the basal ganglia and the cortex. PPTg provides outputs to the dopamine neurons in the midbrain and in turn receives reward-related signals from the cerebral cortices and basal ganglia to perform reinforcement learning. I will discuss representation at PPTg and composition at the dopamine neuron of reward prediction error signal, an important component signal, which induces reward conditioning and motivation during exploratory behavior.