Yoshiko Honda

Enhancement of acetylcholine release during paradoxical sleep in the dorsal tegmental field of the cat brain stem

Acetylcholine (ACh) in the brain stem has been implicated in the generation of paradoxical sleep (PS). In order to clarify the relationship between local ACh release in the dorsal tegmental field (FTD), a possible PS-generating locus, and sleep-wake states in 6 cats. ACh was measured by the method of in vivo microdialysis and high performance liquid chromatography-electrochemical detection. It is noteworthy that ACh release was about 2 times higher (P less than 0.001) during PS than during slow-wave sleep and wakefulness in FTD, but not in the caudate nucleus, a control region. ACh release in FTD appeared to begin to increase prior to the onset of PS. Electrical and chemical (glutamate) stimulations of the nucleus magnocellularis (MC) enhanced ACh release in FTD and shortened PS latency. These results suggest that this PS-related enhancement of ACh release in FTD is induced by some cholinergic projections from glutamate-receptive neurons in MC.

Organization of connectivity of the rat presubiculum: I. Efferent projections to the medial entorhinal cortex

The organization of the laminar and topographical projections from the presubiculum to the entorhinal area was studied in the rat by anterograde labeling with Phaseolus vulgaris leucoagglutinin and retrograde labeling with horseradish peroxidase conjugated to wheat germ agglutinin. We found that the pattern of presubiculo‐entorhinal projections differs between the superficial and deep layers of the presubiculum. The superficial layers (layers II and III) of the presubiculum gave rise to bilateral projections to layers I–VI of the medial entorhinal area (MEA). Many terminals were distributed in layer III, fewer in layer II and the deep portion of layer I, and many fewer terminals in the deep layers (layers V and VI) of MEA. In contrast, the deep layers (layers V and VI) of the presubiculum gave rise to ipsilateral projections to the entorhinal area. Many axon terminals were distributed in layers V and VI of MEA and the most superficial portion of layer I of MEA, but very few in layers II and III. In addition, the ramifications in layer I extended to the lateral entorhinal area (LEA). Using two‐dimensional unfolded maps of parahippocampal cortices, we elucidated the distinct topographical relationship in the presubiculo‐entorhinal projection: 1) The septotemporal or longitudinal axis of the presubiculum corresponded to the axis on the MEA/LEA boundary, where the septal presubiculum projected toward the rhinal fissure and the temporal presubiculum projected away from the fissure. 2) The proximodistal axis of the presubiculum corresponded to the axis from the MEA/LEA boundary to the MEA/parasubiculum boundary that was virtually perpendicular to the MEA/LEA boundary, where the proximal portion of the presubiculum (close to the subiculum) projected to the region near the MEA/LEA boundary. J. Comp. Neurol. 473:463–484, 2004.

CSF histamine levels in rats reflect the central histamine neurotransmission

Reduced cerebrospinal fluid (CSF) histamine levels were found in human hypersomnia. To evaluate the functional significance of changes in CSF histamine levels, we measured the levels in rats across 24h, after the administration of wake-promoting compounds modafinil, amphetamine, and thioperamide, and after sleep deprivation and food deprivation. Thioperamide significantly increased CSF histamine levels with little effects on locomotor activation. Both modafinil and amphetamine markedly increased the locomotor activity, but had no effects on histamine. The levels are high during active period and are markedly elevated by sleep deprivation, but not by food deprivation. Our study suggests that CSF histamine levels in rats reflect the central histamine neurotransmission and vigilance state changes, providing deeper insight into the human data.

Acetylcholine and glutamate release during sleep-wakefulness in the pedunculopontine tegmental nucleus and norepinephrine changes regulated by nitric oxide

Cholinergic neurons in the pons appear to play a major role in generating rapid eye movement (REM) sleep. In the present study, acetylcholine and glutamate release in the pedunculopontine tegmental nucleus (PPT) during the sleep–waking cycle were investigated by in vivo microdialysis. Acetylcholine release during slow wave sleep (SWS) was significantly lower (P < 0.05) than during REM sleep and wakefulness. On the other hand, glutamate release during wakefulness was higher (P < 0.05) than during REM sleep and SWS. Furthermore, the application of N‐methyl‐D‐aspartate (1 mM) induced a significant increase of nitric oxides (NOx) for 20 min (P < 0.05) and a decrease of norepinephrine for the first 15 min (P = 0.01), indicating NOx regulation on norepinephrine release in PPT.

Pael receptor is involved in dopamine metabolism in the nigrostriatal system

Pael receptor (Pael-R) has been identified as one of the substrates of Parkin, a ubiquitin ligase responsible for autosomal recessive juvenile Parkinsonism (AR-JP). When Parkin is inactivated, unfolded Pael-R accumulates in the endoplasmic reticulum and results in neuronal death by unfolded protein stress, suggesting that Pael-R has an important role in the pathogenesis of AR-JP. Here we report the analyses on Pael-R-deficient (KO) and Pael-R-transgenic (Tg) mice. The striatal dopamine (DA) level of Pael-R KO mice was only 60% of that in normal mice, while in Pael-R Tg mice, striatal 3,4-dihydroxyphenylacetic acid (DOPAC) as well as vesicular DA content increased. Moreover, the nigrostriatal dopaminergic neurons of Pael-R Tg mice are more vulnerable to Parkinsons disease-related neurotoxins while those of Pael-R KO mice are less. These results strongly suggest that the Pael-R signal regulates the amount of DA in the dopaminergic neurons and that excessive Pael-R expression renders dopaminergic neurons susceptible to chronic DA toxicity.

Patterns of axonal collateralization of single layer V cortical projection neurons in the rat presubiculum

The presubiculum is one of the important regions of the parahippocampal area known to be responsible for processing and integrating spatial representation information. To understand better the functional roles played by the presubiculum, it is essential to elucidate how output signals from the presubiculum distribute to its target regions. In the present study, the axonal branching patterns of single pyramidal neurons in layer V of the rat presubiculum were investigated by using in vivo injection of a viral vector expressing membrane‐targeted palmitoylation site‐attached green fluorescent protein. We found that individual layer V neurons provide axonal branches to one or two cortical areas with one or more recurrent collaterals to the presubiculum. These neurons were classified into six types, based on their axonal collateralization pattern: neurons with axon branches to 1) both the retrosplenial granular cortex and the parasubiculum, 2) both the retrosplenial granular cortex and the subiculum, and 3) both the medial entorhinal area and the subiculum, and neurons with axonal branches terminating only in 4) the retrosplenial granular cortex, 5) the subiculum, and 6) the presubiculum. Types 1–5 also provide recurrent axons to the presubiculum. Our data demonstrate that layer V of the presubiculum consists of at least six types of cortical projection neurons with various patterns of axonal collateralization. These findings suggest that single presubicular layer V neurons may distribute information to one or two cortical areas participating in the neural circuitry of spatial representation and also send such information back to the presubiculum itself. J. Comp. Neurol. 519:1395–1412, 2011.

Optical Mapping of the Functional Organization of the Rat Trigeminal Nucleus: Initial Expression and Spatiotemporal Dynamics of Sensory Information Transfer during Embryogenesis

We examined the functional organization of the rat trigeminal nuclear complex and its developmental dynamics using a multiple-site optical recording technique. Brainstem preparations were dissected from embryonic day 12 (E12)-E16 rat embryos, and stimulation was applied individually to the three branches of the trigeminal nerve (V1-V3). The action potential activity of presynaptic fibers was detected from E13, and the glutamate-mediated postsynaptic response was significantly observed from E15 on. At E14, the evoked signals usually consisted of only the action potential-related fast component. However, when extracellular Mg2+ was removed, a significant dl-2-amino-5-phosphonovaleric acid-sensitive slow component appeared. These results suggest that postsynaptic function mediated by NMDA receptors is latently generated as early as E14. The response area of the three branches of the trigeminal nerve showed some functional somatotopic organization, with the ophthalmic (V1) nerve area medially located and the mandibular (V3) nerve area laterally located. The center of the trigeminal nuclear complex in which the activity of neurons and synaptic function was greatest shifted caudally with development, suggesting that the functional architecture of the trigeminal nuclear complex is not fixed but changes dynamically during embryogenesis. By electron microscopy, we could not observe clear correlations between functional data and morphological information; when we surveyed E16 preparations, we could not identify typical synaptic structures between the 1,1′-dioctyldecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate-labeled trigeminal nerve terminals and the neurons in the trigeminal nuclear complex. This implies that postsynaptic function in the trigeminal nuclear complex is generated before the appearance of the morphological structure of conventional synapses.

Glial Dysfunction Causes Age-Related Memory Impairment in Drosophila

Several aging phenotypes, including age-related memory impairment (AMI), are thought to be caused by cumulative oxidative damage. In Drosophila, age-related impairments in 1 hr memory can be suppressed by reducing activity of protein kinase A (PKA). However, the mechanism for this effect has been unclear. Here we show that decreasing PKA suppresses AMI by reducing activity of pyruvate carboxylase (PC), a glial metabolic enzyme whose amounts increase upon aging. Increased PC activity causes AMI through a mechanism independent of oxidative damage. Instead, increased PC activity is associated with decreases in D-serine, a glia-derived neuromodulator that regulates NMDA receptor activity. D-serine feeding suppresses both AMI and memory impairment caused by glial overexpression of dPC, indicating that an oxidative stress-independent dysregulation of glial modulation of neuronal activity contributes to AMI in Drosophila.

Acetylcholine releases of mesopontine pgo-on cells in the lateral geniculate nucleus in sleep-waking cycle and serotonergic regulation

1. Five adult cats were prepared with standard sleep-recording electrodes, microinjection cannulae in the bilateral mesopontine tegmentum X area and cannulae for microdialysis probes in the LGN. 2. Dialysates were collected at 5 min intervals during SWS, REM sleep and wakefulness, and during pre- and post-stimulation periods of 5MeODMT microinjection in the bilateral mesopontine tegmentum of freely moving cats. 3. A REM sleep-specific increase of ACh release was observed in the LGN, but not out of the LGN. 4. ACh release was depressed up to 33% by bilateral 5MeODMT microinjection in the mesopontine tegmentum where the microinjection of carbachol also depressed ACh in the LGN probably by stimulating the auto receptor. 5. Our observations indicate that PGO-on neurons of mesopontine tegmentum release more ACh in the LGN during REM sleep by burst discharge than during wakefulness and SWS, and that presumptive cholinergic PGO-on cells are regulated by serotonergic inputs.

Organization of intrinsic connections of the retrosplenial cortex in the rat

The retrosplenial cortex consists of areas 29a–d, each of which has different connections with other cortical and subcortical regions. Although these areas also make complex interconnections that constitute part of a neural circuit subserving various functions, such as spatial memory and navigation, the details of such interconnections have not been studied comprehensively. In the study reported here, we investigated the organization of associational and commissural connections of areas 29a–d within the retrosplenial cortex in the rat, using the retrograde tracer cholera toxin B subunit and anterograde tracer biotinylated dextran amine. The results demonstrated that each of these areas has a distinct set of interconnections within the retrosplenial cortex. Each area interconnects strongly along the transverse axis of the retrosplenial cortex: area 29a, area 29b, caudal area 29c, and caudal area 29d connect with each other, and rostral area 29c and rostral area 29d connect with each other. In the longitudinal direction, rostral-to-caudal projections from rostral areas 29c and 29d to areas 29a and 29b and caudal areas 29c and 29d are strong, whereas reciprocal caudal-to-rostral projections are relatively weak. Although most of the intrinsic connections are homotopical, contralateral connections are weaker and less extensive than ipsilateral connections. These findings suggest that each retrosplenial area may not only process specific information somewhat independently but that it may also integrate and transmit such information through intrinsic connections to other areas in order to achieve retrosplenial cortical functions, such as spatial memory and learning.