Biomedical subjects

Tadashi Isa

Publications and source records attributed to Tadashi Isa.

30 records · Page 2Linked to original sources

PubMed2003

Characteristics of GABAergic neurons in the superficial superior colliculus in mice.

We investigated characteristics of identified GABAergic neurons in slices of the superficial superior colliculus (sSC) using transgenic mice in which green fluorescent protein (GFP) is specifically expressed in GABAergic neurons. Whole-cell patch clamp recordings and intracellular staining with biocytin revealed electrophysiological and morphological properties of GFP-positive neurons. GFP-positive neurons had a tangentially elongated wide dendritic field. In response to depolarizing current pulses, most of the GFP-positive neurons showed either of two firing properties; 55% (n=36/65) generated successive spikes with a constant firing frequency and 22% (n=14/65) showed transient burst firing at a threshold level for spike generation. These results elucidate a functional heterogeneity of GABAergic neurons, and provide fundamental information to understand the function of the GABAergic system in the sSC.

Action Potentials↗

PubMed2003

Local excitatory network and NMDA receptor activation generate a synchronous and bursting command from the superior colliculus.

The generation of bursting spike activity in the deeper layers of the superior colliculus (SC) is a critical determinant of decision making in the initiation of orienting behaviors, such as saccades. The bursting activity exhibits a typical threshold effect that may arise from a nonlinear signal amplification process in the deeper layers of the SC. We used whole-cell patch-clamp recordings in rat SC slices to investigate the neuronal mechanism underlying the generation of such bursting activity. We found that (1) neurons in the intermediate gray layer [stratum griseum intermediale (SGI)] produce a prolonged bursting response when released from GABA(A) receptor-mediated inhibition, (2) this GABA(A) inhibition may partially arise from inhibitory interneurons within the SGI that are driven synaptically by glutamatergic excitatory inputs to the SC, (3) the bursting is not the result of the intrinsic membrane properties of individual SC neurons but is instead produced by local circuits within the SGI, (4) the bursting is mediated by activation of NMDA receptors, and (5) the bursting can be synchronous among SGI neurons. These results suggest that activation of a local excitatory network within the deeper layers of the SC and NMDA receptor-dependent synaptic transmission after release from GABA(A) inhibition are fundamental mechanisms that may explain the nonlinear signal amplification process in the deeper layers of the SC.

Action Potentials↗

PubMed2003

Release from GABA(A) receptor-mediated inhibition unmasks interlaminar connection within superior colliculus in anesthetized adult rats.

The superior colliculus (SC) contains two major subdivisions, the superficial layers (sSC) and the deeper layers (dSC). sSC receives visual information from the retina and visual cortex, while dSC sends descending projections to the brainstem and spinal cord. It has not been clear whether and how sSC directly activates dSC, however recent studies in slice preparations reported that electrical stimulation of sSC induces burst firing in dSC neurons after application of bicuculline. In the present study, we tested whether sSC directly activates dSC in vivo. In isoflurane-anesthetized rats, electrical stimulation of the optic nerve (ON) induced negative field responses mainly in sSC, but not as much in dSC, under control conditions. However, after injection of bicuculline into dSC, ON stimulation induced long-lasting negative field responses in dSC. dSC neurons including the tectofugal neurons exhibited burst firing during the long-lasting negative field responses. The burst responses remained after ablation of the cerebral cortex ipsilateral to the SC recordings. These results suggest that retinal inputs induce burst responses in tectofugal neurons in dSC via subcortical pathways when the SC circuit is released from GABA(A) receptor-mediated inhibition. We propose that sSC is the main candidate for the source of the excitatory synaptic inputs to dSC among the subcortical regions.

Anesthesia↗

PubMed2003

Fulfenamic acid sensitive, Ca(2+)-dependent inward current induced by nicotinic acetylcholine receptors in dopamine neurons.

Nicotinic acetylcholine receptors (nAChRs) exhibit high Ca(2+) permeabilities and the Ca(2+)-influx through the nAChRs may be involved in regulation of a variety of signal processing in the postsynaptic neurons. The mesencephalic dopamine (DA) neurons receive cholinergic inputs from the brainstem and express abundant nAChRs. Here we report that the Ca(2+)-influx induced by a transient pressure application of ACh activates an inward current mediated by nAChRs and subsequently an inward current component that is sensitive to fulfenamic acid (FFA) and phenytoin, presumably a Ca(2+)-activated nonselective cation current in the DA neurons in the midbrain slices of the rat. The FFA- and phenytoin-sensitive current exhibits a negative slope conductance below -40 mV, suggesting its role in significant enhancement of depolarizing responses. In the current clamp recordings with perforated patch clamp configuration, bath application of carbachol markedly enhanced the glutamate-induced depolarization, which led to a long-lasting depolarizing hump. Activation of nAChRs is involved in this process, in cooperation with muscarinic receptors that suppress afterhyperpolarization caused by Ca(2+)-activated K(+)-channels. The long-lasting depolarizing hump was suppressed by FFA. All these results suggested a potential role of the FFA-sensitive current triggered by nAChR activation in marked enhancement of the excitatory synaptic response in DA neurons.

Acetates↗

PubMed2003

Ca2+-dependent inward current induced by nicotinic receptor activation depends on Ca2+/calmodulin-CaMKII pathway in dopamine neurons.

It is well known that midbrain dopamine (DA) neurons receive massive projection from cholinergic neurons in the brainstem. In our preceding report, we showed that Ca(2+)-influx through nicotinic acetylcholine (ACh) receptors in the DA neurons subsequently activated an inward current that was sensitive to fulfenamic acid (FFA) and phenytoin, presumably a Ca(2+)-activated non-selective cation current. The FFA-sensitive current exhibited a negative slope conductance and predominantly enhanced the depolarizing responses of DA neurons. In this study, we showed that the inward FFA-sensitive current was eliminated by antagonists of Ca(2+)/calmodulin (Ca(2+)/CaM), N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide hydrochloride (W-7; 1 microM), trifluoperazine (TFP; 1.5 microM) and calmidazolium (100 nM). Application of W-7 and TFP reduced the ACh-induced inward current and the current component suppressed by these drugs exhibited negative slope conductance, as well as the FFA-sensitive current. Further, intracellular application of KN-93, an antagonist of Ca(2+)/CaM-dependent protein kinase II (CaMKII), but not KN-92 eliminated the FFA-sensitive current. All these results suggest that Ca(2+)/CaM-CaMKII pathway is involved in an activation of the FFA-sensitive current.

Animals↗

PubMed2003

Nigral GABAergic inhibition upon cholinergic neurons in the rat pedunculopontine tegmental nucleus.

We investigated, in a midbrain parasagittal slice preparation of Wistar rats (postnatal day 9-17), the synaptic inhibition of neurons in the pedunculopontine tegmental nucleus (PPN), which was mediated by gamma (gamma)-amino-butyric acid (GABA). Whole-cell patch-clamp recording was used, in combination with a single-cell reverse transcription-polymerase chain reaction amplification technique, to record synaptic potentials and to identify the phenotype of the recorded PPN neuron. In the presence of the ionotropic glutamate receptor antagonists, 6-cyano-2, 3-dihydroxy-7-nitro-quinoxaline-2, 3, dione, and dl-2-amino-5-phosphonovaleric acid, single electrical stimuli were applied to the substantia nigra pars reticulata (SNr), one of the basal ganglia output nuclei. Stimulation of the SNr evoked inhibitory postsynaptic potentials (IPSPs) in 73 of the 104 neurons in the PPN. The IPSPs were abolished with a GABAA receptor antagonist, bicuculline. Inhibitory postsynaptic currents of the neurons were reversed in polarity at approximately -93.5 mV, which was close to the value of the equilibrium potential for chloride ions of -88.4 mV. Single-cell reverse transcription-polymerase chain reactions revealed that approximately 30% (9/32) of the PPN neurons that received inhibition from the SNr expressed detectable levels of choline acetyltransferase mRNA. These findings show that output from the SNr regulates the activity of cholinergic PPN neurons through GABAA receptors.

Animals↗

PubMed2002

Postsynaptic and presynaptic GABA(B) receptor-mediated inhibition in rat superficial superior colliculus neurons.

It has been reported that GABA(B) receptors are abundantly expressed in the superficial superior colliculus (sSC). To elucidate the action of GABA(B) receptors in the sSC, we tested the effect of a specific GABA(B) receptor agonist baclofen on sSC neurons in slices obtained from rats (16-22 days postnatal) using the whole-cell patch clamp technique. Bath application of baclofen (10-30 microM) elicited hyperpolarization associated with an increase in potassium conductance in morphologically different types of neurons including putative excitatory and inhibitory neurons. In addition, baclofen presynaptically suppressed electrically induced excitatory postsynaptic currents and inhibitory postsynaptic currents. These effects of baclofen were antagonized by a specific GABA(B) receptor antagonist CGP55845A (1 microM). The results suggest that the GABA(B) receptors have an inhibitory action at both post- and pre-synaptic sites in the sSC.

Animals↗

PubMed2002

Premotoneuronal and direct corticomotoneuronal control in the cat and macaque monkey.

The literature on premotoneuronal and direct corticomotoneuronal (CM) control in the cat and macaque monkey is reviewed. The available experimental findings are not in accordance with a recently proposed hypothesis that direct CM connections have "replaced" the premotoneuronal pathways. Instead, we propose that premotoneuronal CM control plays an important role in motor control also in primates and that the direct CM connection has been added during phylogeny.

Animals↗

PubMed2002

Brainstem control of head movements during orienting; organization of the premotor circuits.

When an object appears in the visual field, animals orient their head, eyes, and body toward it in a well-coordinated manner (orienting movement). The head movement is a major portion of the orienting movement. Interest in the neural control of head movements in the monkey and human have increased in the 1990's, however, fundamental knowledge about the neural circuits controlling the orienting head movement continues to be based on a large number of experimental studies performed in the cat. Thus, it is crucial now to summarize information that has been clarified in the cat for further advancement in understanding the neural control of head movements in different animal species. The superior colliculus (SC) has been identified as the primary brainstem center controlling the orienting. Its output signal is transmitted to neck motoneurons via two major separate pathways: one through the reticulospinal neurons (RSNs) in the pons and medulla and the other through neurons in Forel's field H (FFH) in the mesodiencephalic junction. The tecto-reticulo-spinal pathway controls orienting chiefly in the horizontal direction, while the tecto-FFH-spinal pathway controls orienting in the vertical direction. In each pathway, a subgroup of neurons functions as premotor neurons for both extraocular and neck motoneurons, while others are specified for each, which allows both coordinated and separate control of eye and head movements. Head movements almost always produce shifts in the center of gravity that might cause postural disturbances. The postural equilibrium may be maintained by transmitting the orienting command to the limb segments via descending axons of the reticulospinal and long propriospinal neurons. The SC and brainstem relay neurons receive descending inputs from higher order structures such as the cerebral cortex, cerebellum, and basal ganglia. These inputs may serve context-dependent control of orienting by modulating the activities of the primary brainstem pathways.

Animals↗

PubMed2002

Intrinsic processing in the mammalian superior colliculus.

The mammalian superior colliculus receives visual inputs from the retina and primary visual cortex in its superficial layers and sends descending motor commands from its deeper layers. It is now becoming clear that a connection exists between these layers, but the signal transmission through it is not robust. The induction of burst discharges in the deeper layer neurons by direct visual inputs from the superficial layers may lead to 'express' saccadic eye movements with extremely short reaction times in behaving animals.

Action Potentials↗

PubMed2002

Contribution of pedunculopontine tegmental nucleus neurons to performance of visually guided saccade tasks in monkeys.

The cholinergic pedunculopontine tegmental nucleus (PPTN) is one of the major ascending arousal systems in the brain stem and is linked to motor, limbic, and sensory systems. Based on previous studies, we hypothesized that PPTN would be related to the integrative control of movement, reinforcement, and performance of tasks in behaving animals. To investigate how PPTN contributes to the behavioral control, we analyzed the activity of PPTN neurons during visually guided saccade tasks in three monkeys in relation to saccade preparation, execution, reward, and performance of the task. During visually guided saccades, we observed saccade-related burst (26/70) and pause neurons (19/70), indicating that a subset of PPTN neurons are related to both saccade execution and fixation. Burst neurons exhibited greater selectivity for saccade direction than pause neurons. The preferred directions for both burst and pause neurons were not aligned with either horizontal or vertical axes, nor biased strongly in either the ipsilateral or the contralateral direction. The spatial representation of the saccade-related activity of PPTN neurons is different from other brain stem saccade systems and may therefore relay saccade-related activity from different areas. Increasing discharges were observed around reward onset in a subset of neurons (22/70). These neurons responded to the freely delivered rewards within ~140 ms. However, during the saccade task, the latencies of the responses around reward onset ranged between 100 ms before and 200 ms after the reward onset. These results suggest that the activity observed after appropriate saccade during the task may include response associated with reward. We found that the reaction time to the appearance of the fixation point (FP) was longer when the animal tended to fail in the ensuring task. This reaction time to FP appearance (RTFP) served as an index of motivation. The RTFP could be predicted by the neuronal activity of a subset of PPTN neurons (13/70) that varied their activity levels with task performance, discharging at a higher rate in successful versus error trials. A combination of responses related to saccade execution, reward delivery, and task performance was observed in PPTN neurons. We conclude from the multimodality of responses in PPTN neurons that PPTN may serve as an integrative interface between the various signals required for performing purposive behaviors.

Animals↗

PubMedDate not supplied

Sensory-motor gating and cognitive control by the brainstem cholinergic system.

As an essential component of ascending activating systems, cholinergic neurons with diffuse projections are supposed to be involved in the regulation of cognitive processes such as attention, consciousness, learning, and memory. As for the role of cholinergic projections from the basal forebrain nuclei to cerebral cortical regions including hippocampus, a couple of models have been proposed that acetylcholine facilitates extrinsic inputs to the cortex and inhibits intracortical processing. In this review, to explore the possibility that there exists a generalized principle on the role of cholinergic systems in the brain, we summarized the knowledge so far obtained on the action of a brainstem cholinergic nucleus, the pedunculopontine tegmental nucleus (PPTN) at their target regions. By in vitro experiments we clarified that cholinergic inputs to the intermediate layer of the superior colliculus, presumably originating from the PPTN, facilitate generation of its motor outputs for the initiation of saccades. Furthermore, cholinergic inputs may enhance excitatory responses of mesopontine dopaminergic cells, for instance to reward-related signals. In addition, we observed that PPTN neurons showed multi-modal activities in behaving monkeys; their activities were related to execution and preparation of saccades, the level of task performance, and reward. The multi-modal activities encoded in the PPTN may suggest that PPTN associates movement-related activities with those related to task performance and reward. Together with the already reported facilitatory action on the sensory processing at the visual thalamus, these observations suggest that the brainstem cholinergic system facilitates the central processes for motor command generation and extrinsic sensory processing. For our final goal of exploring the general working principle of the cholinergic systems, further studies are needed to clarify the effects of the brainstem cholinergic system on the intrinsic processing in the brain.

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