Yasuhiko Tamai

Auditory thalamic nuclei projections to the temporal cortex in the rat

Thalamocortical projections from the auditory thalamic nuclei were examined systematically in the rat, including those from the dorsal division (MGD) of the medial geniculate body (MG), which were less clearly determined in previous studies. Injections of biocytin confined in each thalamic nucleus revealed characteristic features of projections in terms of cortical areas and layers of termination. In contrast to exclusively selective projections to cortical area Te1 from the ventral division (MGV) of the MG, diffuse and selective terminations were observed in the projections from the dorsal (MGD) and medial divisions (MGM) of the MG and the suprageniculate nucleus (SG). Diffuse termination was continuous in layer I or VI of the temporal cortex, while selective termination was in layers III and IV of discrete cortical areas. In addition to diffuse termination in the upper half of layer I of cortical areas Te1, Te2d and Te3v, the MGD and SG projections formed plexuses of axons selectively in lower layer III and layer IV of Te2d and Te3v. The SG projections targeted further the dorsal bank of the perirhinal cortex (PRh), while the MGD projections targeted in part the ventral fringe of Te1. The MGM projections terminated diffusely in layer VI of Te1 and Te3v, and selectively in lower layer III and layer IV of the rostral part of Te3v. Diffuse projections to layers I and VI from the SG and MGM extended in cortical regions over the dorsal fringe of Te1. Selective dense projections to middle cortical layers of Te2d and Te3v (especially its rostral part) indicate the existence of auditory areas, which could be involved in cross-modal interaction with visual and somatosensory system, respectively. Diffuse projections are supposed to bind information processings in these areas and the primary auditory area (Te1).

Pathway of the blink reflex in the brainstem of the cat: interneurons between the trigeminal nuclei and the facial nucleus.

Blink reflex responses evoked by electrical stimulation of the supraorbital nerve were examined using cats and the pathway of the blink reflex in the brainstem was elucidated. Both early response (ER) and late response (LR) were mediated by the main sensory trigeminal nucleus and the spinal trigeminal nucleus. However, a lesion of the main sensory trigeminal nucleus had less effect on the blink reflex than a lesion of the spinal trigeminal nucleus. The ER was mediated not only by the shorter disynaptic pathway of 3 neurons through the trigeminal nerve, the trigeminal nuclei and the facial nucleus but also by a polysynaptic pathway of 4 neurons. The interneurons were located between the trigeminal nuclei and the facial nucleus. Some of these interneurons participated in the production of both ER and LR. The area of the brainstem responsible for ER and LR of the blink reflex was the reticular formation from the rostral part of the medulla to the pons except the medial area around the median sulcus. The LR interneurons were distributed more widely than the ER interneurons.

Topography of projections from the primary and non-primary auditory cortical areas to the medial geniculate body and thalamic reticular nucleus in the rat

The functional significance of parallel and redundant information processing by multiple cortical auditory fields remains elusive. A possible function is that they may exert distinct corticofugal modulations on thalamic information processing through their parallel connections with the medial geniculate body and thalamic reticular nucleus. To reveal the anatomical framework for this function, we examined corticothalamic projections of tonotopically comparable subfields in the primary and non-primary areas in the rat auditory cortex. Biocytin was injected in and around cortical area Te1 after determining best frequency at the injection site on the basis of epicortical field potentials evoked by pure tones. The rostral part of area Te1 (primary auditory area) and area temporal cortex, area 2, dorsal (Te2D) (posterodorsal auditory area) dorsal to the caudal end of area Te1, which both exhibited high best frequencies, projected to the ventral zone of the ventral division of the medial geniculate body. The caudal end of area Te1 (auditory area) and the rostroventral part of area Te1 (a part of anterior auditory field), which both exhibited low best frequencies, projected to the dorsal zone of the ventral division of the medial geniculate body. In contrast to the similar topography in the projections to the ventral division of the medial geniculate body, collateral projections to the thalamic reticular nucleus terminated in the opposite dorsal and ventral zones of the lateral and middle tiers of the nucleus in each pair of the tonotopically comparable cortical subfields. In addition, the projections of the non-primary cortical subfields further arborized in the medial tier of the thalamic reticular nucleus. The results suggest that tonotopically comparable primary and non-primary subfields in the auditory cortex provide corticofugal excitatory effects to the same part of the ventral division of the medial geniculate body. On the other hand, corticofugal inhibition via the thalamic reticular nucleus may operate in different parts of the ventral division of the medial geniculate body or different thalamic nuclei. The primary and non-primary cortical auditory areas are presumed to subserve distinct gating functions for auditory attention.

Topography of corticothalamic projections from the auditory cortex of the rat.

Corticothalamic projections from cortical auditory field to the medial geniculate body (MG) in the rat were systematically examined by making small injections of biocytin in cortical area Te1. All injections, confined to 400 microm in diameter, resulted in two projections terminating in the ventral (MGV) and dorsal divisions (MGD) of the MG. The projections to the MGV were evidently topographic. The rostral and caudal portions of area Te1 projected to the ventromedial and dorsolateral parts of the MGV, respectively, forming narrow bands of terminal axons that extended in the mediolateral direction in the coronal plane of the MGV. The minimum dorsoventral width of the bands ranged approximately from 100 to 300 microm. Besides, the more rostral portion of area Te1 tended to project to the more rostral side of the MGV. The projections to the MGD consistently arborized in its ventral margin made up of the deep dorsal nucleus of the MGD. A similar weak topography along the rostrocaudal direction was observed in the projections to the MGD. Large terminals were occasionally found in the MGD after the injections involving cortical layer V. The distribution of large terminals also appeared topographic along with small terminals that were the major component of labeling. Collaterals of labeled axons produced slabs of terminal field in the thalamic reticular nucleus, which also exhibited a weak topography of distribution. These results provide insights into the structural basis of corticofugal modulations related to the tonotopic organizations in the cortex and MG.

Axonal projections of single auditory neurons in the thalamic reticular nucleus: implications for tonotopy-related gating function and cross-modal modulation.

Tonotopically comparable subfields of the primary auditory area (AI) and nonprimary auditory areas (non‐AI), i.e. posterodorsal area (PD) and ventral auditory area (VA), in the rat cortex have similar topographies in the projection to the ventral division of the medial geniculate nucleus (MGV), but reverse topographies in the projection to the thalamic reticular nucleus (TRN). In this study, we examined axonal projections of single auditory TRN cells, using juxtacellular recording and labeling techniques, to determine features of TRN projections and estimate how the TRN mediates corticofugal inhibition along with the reverse topographies of cortical projections to the TRN. Auditory TRN cells sent topographic projections to limited parts of the MGV in a manner that relays cortical inputs from tonotopically comparable subfields of the AI and non‐AI (PD and VA) to different parts of the MGV. The results suggest that corticofugal excitations from the AI and non‐AI modulate thalamic cell activity in the same part of the MGV, whereas corticofugal inhibitions via the TRN modulate cell activity in different parts of the MGV with regard to tonotopic organization. The AI and non‐AI could serve distinctive gating functions for auditory attention through the differential topography of inhibitory modulation. In addition, we obtained an intriguing finding that a subset of auditory TRN cells projected to the somatosensory but not to the auditory thalamic nuclei. There was also a cell projecting to the MGV and somatosensory nuclei. These findings extend the previously suggested possibility that TRN has a cross‐modal as well as an intramodal gating function in the thalamus.

Efferent connections of the ventral auditory area in the rat cortex: Implications for auditory processing related to emotion

In the rat auditory cortex, ventral (VA) and posterodorsal (PD) areas are the two major auditory fields that receive thalamic afferents from the dorsal division of the medial geniculate body (MGD). VA and PD are presumed to serve distinct functions in tandem as the pair of major cortical recipients of extralemniscal thalamic inputs. To deduce the functional significance of VA, efferent connections of VA were examined with the anterograde tracer biocytin. VA lies primarily in the ventral margin of area Te1 and represents frequencies primarily < 15 kHz [Donishi, T., Kimura, A., Okamoto, K. & Tamai, Y. (2006) Neuroscience, 141, 1553–1567.] Biocytin was iontophoretically injected into cortical regions which were defined as VA based on histological location, auditory response and thalamocortical connectivity. Anterograde labelling revealed two important aspects of cortical projections. First, VA sent a projection to a well‐confined region in the caudal end of the insular cortex (Ins) pivotal for fear memory formation during aversive conditioning. Second, VA sent parallel projections to cortical regions that probably comprise the other nonprimary auditory fields, including PD. The results suggest that VA relays auditory input from the MGD to the Ins for affective memory formation and at the same time dispatches the auditory signal, which may represent emotional content, to the remaining nonprimary auditory fields. PD is assumed to play a pivotal role in auditory spatial processing for directed attention ( Kimura et al., 2004 ). As the counterpart of PD, VA is assumed to give rise to another major stream of cortical information processing, most probably related to emotion.

Sensory response of cortical neurons in the anterior ectosylvian sulcus, including the area evoking eye movement

The deep cortical tissue in the caudal portion of the anterior ectosylvian sulcus (AES) of cats anesthetized with alpha-chloralose was explored to examine the sensory response properties of neurons in this area, which is known to contain an area evoking eye movement. Of 873 neurons isolated, 262 (30.0%) were multimodal, i.e. responsive to two or more of the stimulus modalities of visual, auditory, or somatic. The ratio of multimodal neurons to total neurons in the eye-movement-evoking area was significantly larger than this ratio in other areas; 79 (39.5%) of 200 neurons in the eye-movement-evoking area were multimodal, while 183 (27.2%) of 673 neurons in other areas were multimodal. Neuronal minimal latency in response to visual stimulation was widely and bimodally distributed, showing two peaks at 35 ms and 60 ms, whereas latencies to auditory and somatic stimulation were narrowly distributed, with one peak at 10 ms and 15 ms, respectively. There was no remarkable difference either between unimodal neurons and multimodal neurons or between the neurons in the eye-movement-evoking area and those in other areas in distribution of latency. That there was a significant difference in ratio of multimodal to total neurons between the eye movement area and other areas suggests that some convergence or integration of different kinds of sensory input in relation to eye movement might be carried out in the caudal portion of the AES.

Eye movements following cortical stimulation in the ventral bank of the anterior ectosylvian sulcus of the cat

Eye movements were induced by stimulating the ventral bank of the anterior ectosylvian sulcus (AES) of chloralose-anesthetized cats. Intracortical microstimulation of this cortex evoked centering movements of both eyes. The latency of eye movement was 45 ms (range 40-60 ms) and the intensity of stimulation was 33 microA (range 20-45 microA). The evoked eye movements persisted after ablation of the classical frontal eye field of both sides. These results suggest that the ventral bank of the AES is involved in the control of eye movements.

Activation of central 5HT2A receptors reduces the craniofacial nociception of rats.

We assessed the contribution of central 5HT2A receptors to the craniofacial tissue nociception in naïve male rats. First, we tested whether activation of central 5HT2A receptors affected nociceptive neural activities recorded from superficial laminae of the trigeminal subnucleus caudalis (Vc)/upper cervical spinal cord junction (Vc/C2) region. Two types of units, such as deep-nociceptive or skin-wide dynamic range (WDR) units were identified from extracellular recordings. Topical administration of 5HT2A receptor agonist, (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) onto the Vc/C2 region significantly reduced deep-nociceptive unit discharges evoked by formalin injection into the masseter muscle. Noxious pinch stimulation to the facial skin-evoked skin-WDR unit discharges was significantly reduced by topical administration of 0.1 mg/rat DOI onto the Vc/C2 region. Second, we tested whether i.c.v. administration of DOI affected Fos-like immunoreactivity (-LI) evoked by formalin injection into the masseter muscle. Fos-LI was significantly induced mainly at the ventrolateral (vl) area of trigeminal subnucleus interpolaris (Vi)/Vc junction (vl-Vi/Vc) region and Vc/C2 region in vehicle-treated rats. Formalin-evoked Fos-LI was significantly reduced in laminae I-II of the Vc/C2, but not vl-Vi/Vc region after i.c.v. administration of DOI. Finally, orofacial nocifensive behavioral activities evoked by formalin injection into the masseter muscle were significantly reduced by intracisternal administration of DOI. These results suggest that 5HT2A receptors in the Vc/C2 region mediate antinociceptive effects in the craniofacial nociception.

The role of peripheral 5HT2A and 5HT1A receptors on the orofacial formalin test in rats with persistent temporomandibular joint inflammation.

The role of peripheral serotonin (5HT) 2A and 5HT1A receptors on the orofacial nocifensive behavioral activities evoked by the injection of formalin into the masseter muscle was evaluated in the rats with persistent temporomandibular joint (TMJ) inflammation evoked by Complete Freunds Adjuvant (CFA). The orofacial nocifensive behavioral activities evoked by the injection of formalin into masseter muscle were significantly enhanced at 1 day (CFA day 1 group) or 7 days (CFA day 7 group) during TMJ inflammation. Pretreatment with local administration of 5HT2A receptor antagonist, ketanserin (0.01, 0.1 mg/rat) into the masseter muscle or systemic administration of ketanserin via i.p. injection (1 mg/kg) reduced the orofacial nocifensive behavioral activities of the late phase evoked by formalin injection into masseter muscle on the side of TMJ inflammation (CFA day 7 group). However, local (0.001-0.1 mg/rat) or systemic (1 mg/kg) administration of 5HT1A receptor antagonist, propranolol, into masseter muscle did not produce the antinociceptive effect in CFA day 7 group. Moreover, local administration of ketanserin (0.1 mg) or propranolol (0.1 mg) into masseter muscle did not inhibit nocifensive orofacial behavior in rats without TMJ inflammation. These data suggest that persistent TMJ inflammation causes the elevation of the orofacial nocifensive behavior, and peripheral 5HT2A receptors play an important role in mediating the deep craniofacial tissue nociception in rats with TMJ inflammation.