Riichi Kajiwara

Entorhinal-Hippocampal Interactions Revealed by Real-Time Imaging

The entorhinal cortex provides the major cortical input to the hippocampus, and both structures have been implicated in memory processes. The dynamics of neuronal circuits in the entorhinal-hippocampal system were studied in slices by optical imaging with high spatial and temporal resolution. Reverberation of neural activity was detected in the entorhinal cortex and was more prominent when the inhibition due to γ-aminobutyric acid was slightly suppressed. Neural activity was transferred in a frequency-dependent way from the entorhinal cortex to the hippocampus. The entorhinal neuronal circuit could contribute to memory processes by holding information and selectively gating the entry of information into the hippocampus.

Voltage-sensitive dye versus intrinsic signal optical imaging : comparison of optically determined functional maps from rat barrel cortex

Using intrinsic and voltage-sensitive dye optical imaging methods, somatosensory-evoked neural activity and the consequent metabolic activity were visualized in the barrel cortex at high temporal and spatial resolution. We compared maps of neural and metabolic activity from the perspective of spatial distribution in the cortex. There was good agreement between the two functional maps, if the extent of metabolic activity before a prominent increase in cerebral blood volume (CBV) was assessed. This result indicates that oxygen consumption occurs before CBV changes, in approximately the same cortical area as that in which the preceding neural activity was evoked. This also suggests that the intrinsic signal reflects subthreshold synaptic activity, as well as spiking activity, which is similar to the dye-related signals.

Olfactory input to the parahippocampal region of the isolated guinea pig brain reveals weak entorhinal-to-perirhinal interactions.

The processing of olfactory inputs by the parahippocampal region has a central role in the organization of memory in mammals. The olfactory input is relayed to the hippocampus via interposed synapses located in the piriform and entorhinal cortices. Whether olfactory afferents directly or indirectly project to other areas of the parahippocampal region beside the entorhinal cortex (EC) is uncertain. We performed an electrophysiological and imaging study of the propagation pattern of the olfactory input carried by the fibres that form the lateral olfactory tract (LOT) into the parahippocampal region of the in vitro isolated guinea pig preparation. Laminar analysis was performed on field potential depth profiles recorded with 16‐channel silicon probes at different sites of the insular–parahippocampal cortex. The LOT input induced a large amplitude polysynaptic response in the lateral EC. Following appropriate LOT stimulation, a late response generated by the interposed activation of the hippocampus was observed in the medial EC. LOT stimulation did not induce any local response in area 36 of the perirhinal cortex (PRC), while a small amplitude potential with a delay similar to the lateral EC response was inconsistently observed in PRC area 35. No PRC potentials were observed following the responses evoked by LOT stimulation in either the lateral or the medial EC. These findings were substantiated by current source density analysis of PRC laminar profiles. To further verify the absence of EC‐to–PRC field interactions after LOT stimulation, high‐resolution optical imaging of neuronal activity was performed after perfusion of the isolated brain with the voltage‐sensitive dye RH‐795. The optical recordings confirmed that olfactory‐induced activity in the EC does not induce massive PRC activation. The present findings suggest that the olfactory input into the parahippocampal region is confined to the entorhinal cortex. The results also imply that, as demonstrated for the PRC‐to‐EC pathway, the propagation of neuronal activity from the EC to the PRC is hindered, possibly by a powerful inhibitory control generated within the EC.

Olfactory information converges in the amygdaloid cortex via the piriform and entorhinal cortices: observations in the guinea pig isolated whole-brain preparation

The amygdaloid cortex (AC) has reciprocal connections with the entorhinal cortex (EC) and also receives projections from the olfactory bulb and the piriform cortex (PC). To assess the possibility that the AC and EC represent functionally coupled structures in the olfactory stream of information, we investigated the propagation pattern of neural activity in olfactory cortices − PC, AC and EC − using optical recordings with voltage‐sensitive dyes in the guinea pig in vitro isolated whole‐brain preparation. We observed two distinct pathways that convey neural activation evoked by olfactory nerve stimulation: a medial pathway from the PC to the AC, and a lateral pathway from the PC to the lateral EC along the rhinal sulcus. Besides being activated directly via the medial pathway, the AC was activated a second time via activity that propagated from the lateral EC. Lesion experiments revealed that the lateral pathway close to the rhinal sulcus is crucial for neural activation of the EC. Consistent with this activation pattern, we observed two separate, sharp downward deflections in field potential recordings, and we recorded synaptic potentials with multiple peaks from single neurons in the AC. Our findings suggest that the AC and EC are functionally coupled during olfactory information processing, and that this functional linkage may allow the AC to integrate olfactory sensation with information retained or processed in the EC.

Voltage-Sensitive Dye Imaging of Primary Motor Cortex Activity Produced by Ventral Tegmental Area Stimulation

The primary motor cortex (M1) receives dopaminergic projections from the ventral tegmental area (VTA) through the mesocortical dopamine pathway. However, few studies have focused on changes in M1 neuronal activity caused by VTA activation. To address this issue, we used voltage-sensitive dye imaging (VSD) to reveal the spatiotemporal dynamics of M1 activity induced by single-pulse stimulation of VTA in anesthetized rats. VSD imaging showed that brief electrical stimulation of unilateral VTA elicited a short-latency excitatory–inhibitory sequence of neuronal activity not only in the ipsilateral but also in the contralateral M1. The contralateral M1 response was not affected by pharmacological blockade of ipsilateral M1 activity, but it was completely abolished by corpus callosum transection. Although the VTA-evoked neuronal activity extended throughout the entire M1, we found the most prominent activity in the forelimb area of M1. The 6-OHDA-lesioned VTA failed to evoke M1 activity. Furthermore, both excitatory and inhibitory intact VTA-induced activity was entirely extinguished by blocking glutamate receptors in the target M1. When intracortical microstimulation of M1 was paired with VTA stimulation, the evoked forelimb muscle activity was facilitated or inhibited, depending on the interval between the two stimuli. These findings suggest that VTA neurons directly modulate the excitability of M1 neurons via fast glutamate signaling and, consequently, may control the last cortical stage of motor command processing.

Architecture of odor information processing in the olfactory system

Since the discovery of the superfamily of approximately 1000 odorant receptor genes in rodents, the structural simplicity as well as the complexity of the olfactory system have been revealed. The simple aspects include the one neuron-one receptor rule and the exclusive convergence of projections from receptor neurons expressing the same receptors to one or two glomeruli in the olfactory bulb. Odor decoding in the olfactory cortex or higher cortical areas is likely to be a complicated process that depends on the sequence of signal activation and the relative signal intensities of receptors overlapping for similar but different odors. The aim of the present study was to investigate odor information processing both in receptors and in the olfactory cortex. At the receptor level, the similarity and difference in receptor codes between a pair of chiral odorants were examined using the tissue-printing method for sampling all the epithelial zones. In order to dissect odor-driven signal processing in the olfactory cortex by reducing cross-talk with the non-olfactory activities, such as cyclic respiration or other sensory inputs, an in vitro preparation of isolated whole brain with an attached nose was developed, and the methodologies and resulting hypothesis of receptor-sensitivity-dependent hierarchical odor information coding were reviewed.

Voltage-sensitive dye imaging of intervibrissal fur-evoked activity in the rat somatosensory cortex

The intervibrissal fur-evoked activity in the rat somatosensory cortex was investigated using high-resolution optical imaging with a voltage-sensitive dye. The optical imaging revealed that the intervibrissal fur representation forms a U-shaped band around the borders of the posteromedial barrel subfield (PMBSF), and that this representation is characterized by a rostral-to-caudal somatotopic organization. When GABA(A)-mediated inhibition was partially suppressed by treatment with bicuculline, stimulation of the intervibrissal fur elicited spreading of an excitation wave in an area outside the PMBSF. The spreading wave propagated in both directions along the aforementioned U-shaped band of cortex, but barely invaded the center of the PMBSF. These imaging results suggest a distinct subdivision of cortex adjacent to, but outside, the PMBSF in the rat somatosensory cortex; this region receives input from intervibrissal fur, and seems to process its sensory information through well-developed local horizontal connections.

Optical imaging of rat prefrontal neuronal activity evoked by stimulation of the ventral tegmental area.

Using a voltage-sensitive dye, the spatiotemporal dynamics of prefrontal neuronal activity evoked by electrical stimulation of the ventral tegmental area were visualized through optical imaging in anaesthetized rats. Even single-pulse stimulation of the ventral tegmental area elicited a widespread wave of depolarization followed by hyperpolarization in the dorsomedial shoulder region of the prefrontal cortex. We also examined the contribution of dopaminergic transmission to the optical signals by comparing normal and 6-hydroxydopamine-lesioned rats. The 6-hydroxydopamine lesions of ventral tegmental area resulted in a complete absence of depolarization in the prefrontal cortex, although hyperpolarization was preserved. These results indicate that dopaminergic neurons are needed to generate excitatory responses in the prefrontal cortex.

Repetitive olfactory nerve stimulation induced enhancement of neural activities in the amygdaloid cortex of guinea pig isolated whole brain

whether the body weight level affected enhanced sucrose preference induced by a modified taste-nutrition association paradigm in C57BL/6 male mice. Under daily 19-h water deprivation, food restricted-mice were allowed to consume one of two sweeteners: a caloric 0.15 M sucrose (Suc) in odd days or an artificial non-caloric sweetener, 5 mM sodium saccharin (Sac), in even days (alternative conditioning procedure). As their body weights were reduced to about 80% of their original level, the amount of Suc intake remarkably increased, while that of Sac intake unchanged. When their body weights were recovered to the original level, the preference for Suc was abruptly dropped down to the similar preference level for Sac (Saltatory suppression of Suc preference). The similar result appeared even when separate mouse group were simultaneously given 0.15 M Suc and 5 mM Sac using two-bottle method with the same food restriction. We examined the effects of lesions of the somatosensory area related to four limbs in the cerebral cortex on the saltatory suppression of Suc preference. Lesioned mice did not exhibit the saltatory suppression of Suc preference. In Experiment 2, separate mice group was conditioned to acquire learned aversion to the Suc and were allowed to consume the Suc solution every day with food restriction. Their Suc intake was increased as energetic source to compensate caloric deficiency. However, the Suc intake gradually decreased in a few days after their body weight recovered to their original level, resulting in the preference for Suc lowered to the similar level in ad libitum fed-mice. These results indicate that the integrative neural mechanism controls the caloric sugar preference through neural crosstalk among nutritional need, homeostatic energetic status, taste-related memory and cognitive function.

Stable recording of stimulus-evoked field potentials in the anesthetized rat

Emotion is an essentical property for humans. However, the brain mechanisms of emotion are not fully understood. Especially, negative emotion-related motor phenomenon, such as freezing or startle, has received little attention in humans. We investigated whether the negatively emotional visual stimuli can modulate the human primary motor cortex (M1) activation by using the International Affection Picture System (IAPS) and the transcranial magnetic stimulation (TMS). In addition to the conventional single pulse TMS, we also utilized the paired TMS to evaluate the intracortical inhibitory circuit within M1 (short-latency intracortical inhibition: SICI). We found the increase of cortico-spinal excitability measured by motor evoked potential amplitude and the enhanced SICI associated with negatively emotional stimuli but not with neutral ones. We, for the first time, reported the enhancement of intracortical inhibition by negative emotion, which may be the physiologic correlate of motor deactivation induced by negative emotion.