Parkinson's disease (PD) is a condition in which degeneration of dopamine (DA) containing neurons in the substantia nigra pars compacta leads to motor and cognitive disability. The loss of DA-neurons and their afferents alters neuronal activity of basal ganglia, which are brain areas involved in motor and cognitive control, and impair their information processing mechanism and/or generate improper signals. The most widely accepted theory from the last 15 years is that parkinsonism is due to the imbalance of the two major neuronal pathways in the basal ganglia. The pathways are named as the direct and indirect pathways. The theory assumes that a DA-depletion in the basal ganglia results in a decrease of neuronal activity in the direct pathway and an increase in the indirect pathway. It has become increasingly apparent that when changes in the average firing activity are compared in animal models of PD, the results often do not support this assumption. However, our preliminary data and those of others have strongly suggested that synaptically induced neuronal responses in the direct and indirect pathways were indeed altered in animal models of PD, but the mean firing frequencies were not. However, details of the alterations are still unknown. We believe that the altered synaptic activity is the basis for the abnormal information processes that are associated with abnormal oscillations and synchronization of neuronal activity observed in parkinsonian patients and animals and that this abnormal activity leads to a development of PD. Thus, the proposed physiological and anatomical investigations in primate and rodent model of PD will test the main hypothesis that DA- depletion decreases the gain of the direct and increases the gain of indirect pathways and that the changes of the gains are due to altered synaptic responses, membrane properties, and anatomy of the basal ganglia nuclei the striatum and/or pallidum. The results of proposed investigations will provide new understanding of the flow of signals in the basal ganglia and how the loss of DA affects the neuronal activity patterns and information flow. This information is essential for developing drugs that target specific circuitry involved in the manifestation of parkinsonisms.
A large number of people, up to 25% of aging population over 65 years of age, suffer from Parkinson's disease (PD). This study is to reveal the details of the altered synaptic activity and membrane properties in the basal ganglia and aid developing effective surgical treatments and drugs for PD that target specific circuitry of the basal ganglia, the brain areas involved in motor and cognitive control.
|Kita, Takako; Shigematsu, Naoki; Kita, Hitoshi (2016) Intralaminar and tectal projections to the subthalamus in the rat. Eur J Neurosci 44:2899-2908|
|Kim, Juhyon; Kita, Hitoshi (2015) Posttetanic enhancement of striato-pallidal synaptic transmission. J Neurophysiol 114:447-54|
|Kita, Takako; Osten, Pavel; Kita, Hitoshi (2014) Rat subthalamic nucleus and zona incerta share extensively overlapped representations of cortical functional territories. J Comp Neurol 522:4043-56|
|Kim, Juhyon; Kita, Hitoshi (2013) Short-term plasticity shapes activity pattern-dependent striato-pallidal synaptic transmission. J Neurophysiol 109:932-9|
|Deister, Christopher A; Dodla, Ramana; Barraza, David et al. (2013) Firing rate and pattern heterogeneity in the globus pallidus arise from a single neuronal population. J Neurophysiol 109:497-506|
|Kita, Takako; Kita, Hitoshi (2012) The subthalamic nucleus is one of multiple innervation sites for long-range corticofugal axons: a single-axon tracing study in the rat. J Neurosci 32:5990-9|
|Tachibana, Yoshihisa; Iwamuro, Hirokazu; Kita, Hitoshi et al. (2011) Subthalamo-pallidal interactions underlying parkinsonian neuronal oscillations in the primate basal ganglia. Eur J Neurosci 34:1470-84|
|Nishibayashi, Hiroki; Ogura, Mitsuhiro; Kakishita, Koji et al. (2011) Cortically evoked responses of human pallidal neurons recorded during stereotactic neurosurgery. Mov Disord 26:469-76|
|Jaeger, D; Kita, H (2011) Functional connectivity and integrative properties of globus pallidus neurons. Neuroscience 198:44-53|
|Kita, Hitoshi; Kita, Takako (2011) Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia. J Neurosci 31:10311-22|
Showing the most recent 10 out of 12 publications