Satoshi Ikemoto, Ph.D.

@article{pmid35296648,

title = {Medial prefrontal cortex and anteromedial thalamus interaction regulates goal-directed behavior and dopaminergic neuron activity},

author = {Chen Yang and Yuzheng Hu and Aleksandr D Talishinsky and Christian T Potter and Coleman B Calva and Leslie A Ramsey and Andrew J Kesner and Reuben F Don and Sue Junn and Aaron Tan and Anne F Pierce and Céline Nicolas and Yosuke Arima and Seung-Chan Lee and Conghui Su and Jensine M Coudriet and Carlos A Mejia-Aponte and Dong V Wang and Hanbing Lu and Yihong Yang and Satoshi Ikemoto},

url = {https://pubmed.ncbi.nlm.nih.gov/35296648/},

doi = {10.1038/s41467-022-28892-7},

issn = {2041-1723},

year  = {2022},

date = {2022-03-01},

urldate = {2022-03-01},

journal = {Nat Commun},

volume = {13},

number = {1},

pages = {1386},

abstract = {The prefrontal cortex is involved in goal-directed behavior. Here, we investigate circuits of the PFC regulating motivation, reinforcement, and its relationship to dopamine neuron activity. Stimulation of medial PFC (mPFC) neurons in mice activated many downstream regions, as shown by fMRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. We also found using fMRI in human participants watching reinforcing video clips that there is reciprocal excitatory functional connectivity, as well as co-activation of the two regions. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement, and dopaminergic neuron activity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35227866,

title = {Seeking motivation and reward: Roles of dopamine, hippocampus, and supramammillo-septal pathway},

author = {Andrew J Kesner and Coleman B Calva and Satoshi Ikemoto},

url = {https://pubmed.ncbi.nlm.nih.gov/35227866/},

doi = {10.1016/j.pneurobio.2022.102252},

issn = {1873-5118},

year  = {2022},

date = {2022-02-01},

urldate = {2022-02-01},

journal = {Prog Neurobiol},

volume = {212},

pages = {102252},

abstract = {Reinforcement learning and goal-seeking behavior are thought to be mediated by midbrain dopamine neurons. However, little is known about neural substrates of curiosity and exploratory behavior, which occur in the absence of clear goal or reward. This is despite behavioral scientists having long suggested that curiosity and exploratory behaviors are regulated by an innate drive. We refer to such behavior as information-seeking behavior and propose 1) key neural substrates and 2) the concept of environment prediction error as a framework to understand information-seeking processes. The cognitive aspect of information-seeking behavior, including the perception of salience and uncertainty, involves, in part, the pathways from the posterior hypothalamic supramammillary region to the hippocampal formation. The vigor of such behavior is modulated by the following: supramammillary glutamatergic neurons; their projections to medial septal glutamatergic neurons; and the projections of medial septal glutamatergic neurons to ventral tegmental dopaminergic neurons. Phasic responses of dopaminergic neurons are characterized as signaling potentially important stimuli rather than rewards. This paper describes how novel stimuli and uncertainty trigger seeking motivation and how these neural substrates modulate information-seeking behavior.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33990558,

title = {Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction in mice},

author = {Andrew J Kesner and Rick Shin and Coleman B Calva and Reuben F Don and Sue Junn and Christian T Potter and Leslie A Ramsey and Ahmed F Abou-Elnaga and Christopher G Cover and Dong V Wang and Hanbing Lu and Yihong Yang and Satoshi Ikemoto},

url = {https://pubmed.ncbi.nlm.nih.gov/33990558/},

doi = {10.1038/s41467-021-23040-z},

issn = {2041-1723},

year  = {2021},

date = {2021-05-01},

urldate = {2021-05-01},

journal = {Nat Commun},

volume = {12},

number = {1},

pages = {2811},

abstract = {The supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nicolas:2019aa,

title = {Incubation of Cocaine Craving After Intermittent-Access Self-administration: Sex Differences and Estrous Cycle.},

author = {Celine Nicolas and Trinity I Russell and Anne F Pierce and Steeve Maldera and Amanda Holley and Zhi-Bing You and Margaret M McCarthy and Yavin Shaham and Satoshi Ikemoto},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30846301},

doi = {10.1016/j.biopsych.2019.01.015},

issn = {1873-2402 (Electronic); 0006-3223 (Linking)},

year  = {2019},

date = {2019-06-01},

urldate = {2019-06-01},

journal = {Biol Psychiatry},

volume = {85},

number = {11},

pages = {915--924},

address = {Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland.},

abstract = {BACKGROUND: Studies using continuous-access drug self-administration showed that cocaine seeking increases during abstinence (incubation of cocaine craving). Recently, studies using intermittent-access self-administration showed increased motivation to self-administer and seek cocaine. We examined whether intermittent cocaine self-administration would potentiate incubation of craving in male and female rats and examined the estrous cycle's role in this incubation. METHODS: In experiment 1, male and female rats self-administered cocaine either continuously (8 hours/day) or intermittently (5 minutes ON, 25 minutes OFF x 16) for 12 days, followed by relapse tests after 2 or 29 days. In experiments 2 and 3, female rats self-administered cocaine intermittently for six, 12, or 18 sessions. In experiment 4, female rats self-administered cocaine continuously followed by relapse tests after 2 or 29 days. In experiments 3 and 4, the estrous cycle was measured using a vaginal smear test. RESULTS: Incubation of cocaine craving was observed in both sexes after either intermittent or continuous drug self-administration. Independent of access condition and abstinence day, cocaine seeking was higher in female rats than in male rats. In both sexes, cocaine seeking on both abstinence days was higher after intermittent drug access than after continuous drug access. In female rats, incubation of craving after either intermittent or continuous drug access was significantly higher during estrus than during non-estrus; for intermittent drug access, this effect was independent of the training duration. CONCLUSIONS: In both sexes, intermittent cocaine access caused time-independent increases in drug seeking during abstinence. In female rats, the time-dependent increase in drug seeking (incubation) is critically dependent on the estrous cycle phase.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wang2017,

title = {Disrupting Glutamate Co-transmission Does Not Affect Acquisition of Conditioned Behavior Reinforced by Dopamine Neuron Activation.},

author = {Dong V Wang and Thomas Viereckel and Vivien Zell and Asa Konradsson-Geuken and Carl J Broker and Aleksandr Talishinsky and Ji Hoon Yoo and Melissa H Galinato and Emma Arvidsson and Andrew J Kesner and Thomas S Hnasko and Asa Wallen-Mackenzie and Satoshi Ikemoto},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28297663},

doi = {10.1016/j.celrep.2017.02.062},

issn = {2211-1247 (Electronic)},

year  = {2017},

date = {2017-03-14},

journal = {Cell Rep},

volume = {18},

number = {11},

pages = {2584--2591},

address = {Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.},

abstract = {Dopamine neurons in the ventral tegmental area (VTA) were previously found to express vesicular glutamate transporter 2 (VGLUT2) and to co-transmit glutamate in the ventral striatum (VStr). This capacity may play an important role in reinforcement learning. Although it is known that activation of the VTA-VStr dopamine system readily reinforces behavior, little is known about the role of glutamate co-transmission in such reinforcement. By combining electrode recording and optogenetics, we found that stimulation of VTA dopamine neurons in vivo evoked fast excitatory responses in many VStr neurons of adult mice. Whereas conditional knockout of the gene encoding VGLUT2 in dopamine neurons largely eliminated fast excitatory responses, it had little effect on the acquisition of conditioned responses reinforced by dopamine neuron activation. Therefore, glutamate co-transmission appears dispensable for acquisition of conditioned responding reinforced by DA neuron activation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}