Tonically discharging putamen neurons exhibit set-dependent response
MINORU KIMURA, JANUSZ RAJKOWSKI, AND EDWARD EVARTS
PNAS (1984)
doi: 10.1073/pnas.81.15.4998
Responses of Tonically Active Neurons in the Primate’s Striatum Undergo Systematic Changes during Behavioral Sensorimotor Conditioning
Toshihiko Aosaki, Hiroshi Tsubokawa, Akihiro Ishida, Katsushige Watanabe, Ann M. Graybiel, and Minoru Kimura
The Journal of Neuroscience (1994)
Doi: 10.1523/JNEUROSCI.14-06-03969.1994
Temporal and Spatial Characteristics of Tonically Active Neuronsof the Primate’s Striatum
TOSHIHIKO AOSAKI, MINORU KIMURA, AND ANN M. GRAYBIEL
JOURNAL OF NEUROPHYSIOLOGY (1995)
doi: 10.1152/jn.1995.73.3.1234
Brief summary: in the above studies, Kimura and colleagues found that the tonically active neurons (TANs) in the putamen of monkeys signaled the reward-predictive cues with two activity patterns: a dominant pause-rebound pattern and a burst-pause pattern. The patterns were evolved during the learning of the Pavlovian conditioning. And the TANs were inferred as cholinergic interneurons (ChIs).
The paper in 1984 is the first observation about the response properties of tonically active neurons (nowadays it is believed that they are cholinergic interneurons) in striatum. It was very alike the study in visual system before Hubel and Wiesel. Before their studies, people had no ideas about how the neurons in visual cortex encoded the external stimuli. After many failures, by accident, they observed that neurons in visual cortex shown strong spiking activity to the retracted slides when they were trying to stop the experiments. This was their ‘Aha’ moment in the series classic studies afterwards. Similarly, at the very beginning of the study on many other brain areas, researchers also have no ideas about the directions to commence on. At this phase, the ground breaking findings are at dawn, such as Hubel and Wiesel‘s works about visual system in 1960s, John O’keefe’s works about place cells in 1970s, Ann Graybiel’s works about basal ganglia in 1980s, Schultz’s works about dopamine in 1990s, Goldman-Rakic‘s works about dlPFC in working memory in 1990s, etc. This time is KIMURA‘s works about the TANs in striatum. How they conceived to use Pavlovian conditioning paradigm to test the response properties of TANs? In the another way, what’s the ‘aha’ moment in their studies? The first hint might come from the observations of Parkinson’s patients.
Parkinson’s patients alway shown movements deficits and concomitant cell death in the substantia nigra pars compacta (SNc). Based on anatomical studies, SNc and striatum have strong reciprocal connections. So at first, people reasoned that TANs maybe encode movement related information. Unexpectedly, just as the first finding by Schultz about dopamine neurons, one previous study found that TANs had no strong correlates with movements (Single cell studies of the primate putamen. II. Relations to direction of movement and pattern of muscular activity, Exp Brain Res,1984). So in the 1984’s study, the authors slightly modified the experimental conditions, in which they used the clicks to predict reward. In this way, motivational or saliency information was endowed to the cues. At this time, they successfully observed two stereotyped activity patterns of TANs: burst-pause and pause-rebound patterns. In the 1994’s study, they further found that the patterns were gradually evolved during the learning process of the Pavlovian conditioning and disappeared during extinction after the initial learning. Importantly, they also confirmed that the responses were not related to the licking behaviors. The findings were persuasive. They were the milestones in the journey of dissecting TANs (ChIs). The most striking findings in the 1995’s study was that they inferred the identity of TANs as ChIs based on the density of cell-type specific staining and the cell number recorded within each electrode penetration. It’s quit impressive!
When we look back on the history of scientific discoveries, the most fascinating moment should be the re-discovery of the ‘aha’ moment by previous researchers. Usually the traces which gave birth to the first enlightenment are unnoticeable if only read research papers. So the memoirs or the interviews of senior scientists are of unlimited values for us to ‘retrieve’ those shining moments. But this kind of materials are very scarce. Be appreciative if someday you came across these precious records.