Biomedical subjects

Richard C Saunders

Publications and source records attributed to Richard C Saunders.

14 recordsLinked to original sources

PubMed2005

Projections from the entorhinal cortex, perirhinal cortex, presubiculum, and parasubiculum to the medial thalamus in macaque monkeys: identifying different pathways using disconnection techniques.

The projections from the perirhinal cortex, entorhinal cortex, parasubiculum, and presubiculum to the thalamus were examined using both anterograde and retrograde tracers. Attention focused on the routes taken by these projections, which were delineated by combining surgical tract section with the placement of a tracer. Projections to the anterior thalamic nuclei almost exclusively used the fornix. These relatively light projections, which arose from all areas of the entorhinal cortex, from the presubiculum, parasubiculum, and area 35 of the perirhinal cortex, terminated mainly in the anterior ventral nucleus. In contrast, the projections to the lateral dorsal nucleus from the entorhinal cortex, presubiculum and parasubiculum were denser than those to the anterior thalamic nuclei. The projections to the lateral dorsal nucleus used two routes. While nearly all of the projections from the subicular complex used the fornix, many of the entorhinal cortex projections passed caudally in the temporopulvinar bundle to reach the lateral dorsal nucleus. The perirhinal cortex, as well as the entorhinal cortex, also projects to nucleus medialis dorsalis. These projections exclusively used the external capsule and thence the inferior thalamic peduncle. Other temporal-thalamic projections included those to the medial pulvinar, via the temporopulvinar bundle, from the perirhinal and entorhinal cortices, and those to the paraventricular nucleus from the entorhinal cortex. By identifying these routes, it is possible to appreciate how different lesions might disconnect temporal-diencephalic pathways and so contribute to memory disorders.

Amidines↗

PubMed2005

A conserved mRNA expression profile of SREB2 (GPR85) in adult human, monkey, and rat forebrain.

SREB is a subfamily of G-protein-coupled receptors, which consists of SREB1 (GPR27), SREB2 (GPR85), and SREB3 (GPR173). Its high evolutionary conservation and predominant expression in the CNS suggest that SREB family members and their undiscovered ligand(s) may have significant functions in the nervous system. SREB2 is the most conserved receptor throughout vertebrate evolution. As a first step in understanding the function of the SREB family, we have determined the anatomical gene expression profile of SREB2 in adult human, monkey, and rat forebrain using in situ hybridization histochemistry. The expression pattern of SREB2 mRNA was well conserved across three mammalian species. SREB2 mRNA was expressed in neurons throughout the brain and the most abundant expression was detected in the hippocampal dentate gyrus in all species examined. The areas expressing high levels of SREB2 mRNA overlap with brain structures known to possess high levels of plasticity, namely, the hippocampal formation, olfactory system, and supraoptic and paraventricular nuclei. Further, the anatomical expression of SREB1 and SREB3 overlapped with that of SREB2 in the adult monkey brain. Together, these data suggest a possible link between SREB family and neural plasticity, which may explain its extremely high conservation throughout vertebrate evolution.

Animals↗

PubMed2005

In search of an auditory engram.

Monkeys trained preoperatively on a task designed to assess auditory recognition memory were impaired after removal of either the rostral superior temporal gyrus or the medial temporal lobe but were unaffected by lesions of the rhinal cortex. Behavioral analysis indicated that this result occurred because the monkeys did not or could not use long-term auditory recognition, and so depended instead on short-term working memory, which is unaffected by rhinal lesions. The findings suggest that monkeys may be unable to place representations of auditory stimuli into a long-term store and thus question whether the monkey's cerebral memory mechanisms in audition are intrinsically different from those in other sensory modalities. Furthermore, it raises the possibility that language is unique to humans not only because it depends on speech but also because it requires long-term auditory memory.

Animals↗

PubMed2005

Dynamic circuitry for updating spatial representations. I. Behavioral evidence for interhemispheric transfer in the split-brain macaque.

Internal representations of the sensory world must be constantly adjusted to take movements into account. In the visual system, spatial updating provides a mechanism for maintaining a coherent map of salient locations as the eyes move. Little is known, however, about the pathways that produce updated spatial representations. In the present study, we asked whether direct cortico-cortical links are required for spatial updating. We addressed this question by investigating whether the forebrain commissures-the direct path between the two cortical hemispheres-are necessary for updating visual representations from one hemifield to the other. We assessed spatial updating in two split-brain monkeys using the double-step task, which involves saccades to two sequentially appearing targets. Accurate performance requires that the representation of the second target be updated to take the first saccade into account. We made two central discoveries regarding the pathways that underlie spatial updating. First, we found that split-brain monkeys exhibited a selective initial impairment on double-step sequences that required updating across visual hemifields. Second, and most surprisingly, these impairments were neither universal nor permanent: the monkeys were ultimately able to perform the across-hemifield sequences and, in some cases, this ability emerged rapidly. These findings indicate that direct cortical links provide the main substrate for updating visual representations, but they are not the sole substrate. Rather, a unified and stable representation of visual space is supported by a redundant cortico-subcortical network with a striking capacity for reorganization.

Animals↗

PubMed2005

Dynamic circuitry for updating spatial representations. II. Physiological evidence for interhemispheric transfer in area LIP of the split-brain macaque.

With each eye movement, a new image impinges on the retina, yet we do not notice any shift in visual perception. This perceptual stability indicates that the brain must be able to update visual representations to take our eye movements into account. Neurons in the lateral intraparietal area (LIP) update visual representations when the eyes move. The circuitry that supports these updated representations remains unknown, however. In this experiment, we asked whether the forebrain commissures are necessary for updating in area LIP when stimulus representations must be updated from one visual hemifield to the other. We addressed this question by recording from LIP neurons in split-brain monkeys during two conditions: stimulus traces were updated either across or within hemifields. Our expectation was that across-hemifield updating activity in LIP would be reduced or abolished after transection of the forebrain commissures. Our principal finding is that LIP neurons can update stimulus traces from one hemifield to the other even in the absence of the forebrain commissures. This finding provides the first evidence that representations in parietal cortex can be updated without the use of direct cortico-cortical links. The second main finding is that updating activity in LIP is modified in the split-brain monkey: across-hemifield signals are reduced in magnitude and delayed in onset compared with within-hemifield signals, which indicates that the pathways for across-hemifield updating are less effective in the absence of the forebrain commissures. Together these findings reveal a dynamic circuit that contributes to updating spatial representations.

Animals↗

PubMed2005

Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys.

Excitotoxic lesion studies have confirmed that the rhinal cortex is essential for visual recognition ability in monkeys. To evaluate the mnemonic role of cholinergic inputs to this cortical region, we compared the visual recognition performance of monkeys given rhinal cortex infusions of a selective cholinergic immunotoxin, ME20.4-SAP, with the performance of monkeys given control infusions into this same tissue. The immunotoxin, which leads to selective cholinergic deafferentation of the infused cortex, yielded recognition deficits of the same magnitude as those produced by excitotoxic lesions of this region, providing the most direct demonstration to date that cholinergic activation of the rhinal cortex is essential for storing the representations of new visual stimuli and thereby enabling their later recognition.

Acetylcholine↗

PubMed2005

Corollary discharge and spatial updating: when the brain is split, is space still unified?

How does the brain keep track of salient locations in the visual world when the eyes move? In parietal, frontal and extrastriate cortex, and in the superior colliculus, neurons update or 'remap' stimulus representations in conjunction with eye movements. This updating reflects a transfer of visual information, from neurons that encode a salient location before the saccade, to neurons that encode the location after the saccade. Copies of the oculomotor command - corollary discharge signals - must initiate this transfer. We investigated the circuitry that supports spacial updating in the primate brain. Our central hypothesis was that the forebrain commissures provide the primary route for remapping spatial locations across visual hemifields, from one cortical hemisphere to the other. Further, we hypothesized that these commissures provide the primary route for communicating corollary discharge signals from one hemisphere to the other. We tested these hypotheses using the double-step task and subsequent physiological recording in two split-brain monkeys. In the double-step task, monkeys made sequential saccades to two briefly presented targets, T1 and T2. In the visual version of the task, the representation of T2 was updated either within the same hemifield ("visual-within"), or across hemifields ("visual-across"). In the motor version, updating of the visual stimulus was always within-hemifield. The corollary discharge signal that initiated the updating, however, was generated either within the same hemisphere ("motor-within") or in the opposite hemisphere ("motor-across"). We expected that, in the absence of the forebrain commissures, both visual-across and motor-across conditions would be impaired relative to their "within" controls. In behavioral experiments, we observed striking initial impairments in the monkeys' ability to update stimuli across visual hemifields. Surprisingly, however, both animals were ultimately capable of performing the visual-across sequences of the double-step task. In subsequent physiological experiments, we found that neurons in lateral intraparietal cortex (LIP) can remap stimuli across visual hemifields, albeit with a reduction in the strength of remapping activity. These behavioral and neural findings indicate that the transfer of visual information is compromised, but by no means abolished, in the absence of the forebrain commissures. We found minimal evidence of impairment of the motor-across condition. Both monkeys readily performed the motor-across sequences of the double-step task, and LIP neurons were robustly active when within-hemifield updating was initiated by a saccade into the opposite hemifield. These results indicate that corollary discharge signals are available bilaterally. Altogether, our findings show that both visual and corollary discharge signals from opposite hemispheres can converge to update spatial representations in the absence of the forebrain commissures. These investigations provide new evidence that a unified and stable representation of visual space is supported by a redundant circuit, comprised of cortical as well as subcortical pathways, with a remarkable capacity for reorganization.

Animals↗

PubMed2005

Measurement of regional rates of cerebral protein synthesis with L-[1-11C]leucine and PET with correction for recycling of tissue amino acids: II. Validation in rhesus monkeys.

The confounding effect of recycling of amino acids derived from tissue protein breakdown into the precursor pool for protein synthesis has been an obstacle to adapting in vivo methods for determination of regional rates of cerebral protein synthesis (rCPS) to positron emission tomography (PET). We used a kinetic modeling approach to estimate lambda, the fraction of the precursor pool for protein synthesis derived from arterial plasma, and to measure rCPS in three anesthetized adult monkeys dynamically scanned after a bolus injection of L-[1-11C]leucine. In the same animals, lambda was directly measured in a steady-state terminal experiment, and values showed excellent agreement with those estimated in the PET studies. In three additional monkeys rCPS was determined with the quantitative autoradiographic L-[1-14C]leucine method. In whole brain and cerebellum, rates of protein synthesis determined with the autoradiographic method were in excellent agreement with those determined with PET, and regional values were in good agreement when differences in spatial resolution of the two methods were taken into account. Low intrasubject variability was found on repeated PET studies. Our results in anesthetized monkey indicate that, by using a kinetic modeling approach to correct for recycling of tissue amino acids, quantitatively accurate and reproducible measurement of rCPS is possible with L-[1-11C]leucine and PET.

Amino Acids↗

PubMed2005

Projections from the hippocampal region to the mammillary bodies in macaque monkeys.

A combination of anterograde and retrograde tracers mapped the direct hippocampal and parahippocampal inputs to the mammillary bodies in two species of macaque monkey. Dense projections arose from pyramidal cells in layer III of the subiculum and prosubiculum, and terminated in the medial mammillary nucleus. While there was no evidence of an input from the dentate gyrus or fields CA1-3, a small contribution arose from the presubiculum and entorhinal cortices. All of the hippocampal and parahippocampal projections to the mammillary bodies appeared to use the fornix as a route. The caudal portions of the subiculum and prosubiculum contained the greatest numbers of cells projecting to the mammillary bodies. A light contralateral projection to the medial mammillary nucleus was also observed, although this appeared to arise primarily from the more rostral portions of the subiculum and prosubiculum. There was a crude topography within the medial mammillary nucleus, with the caudal subicular projections terminating in the mid and dorsal portions of the nucleus while the rostral subicular and entorhinal projections terminated in the ventral and lateral portions of the medial nucleus. Light ipsilateral projections throughout the lateral mammillary nucleus were sometimes observed. Comparisons with related studies of the macaque brain showed that the dense hippocampal projections to the mammillary bodies arise from a population of subicular cells separate from those that project to the anterior thalamic nuclei, even though the major output from the mammillary bodies is to the anterior thalamic nuclei. Other comparisons revealed underlying similarities with the corresponding projections in the rat brain.

Amino Acids↗

PubMed2004

DNA targeting of rhinal cortex D2 receptor protein reversibly blocks learning of cues that predict reward.

When schedules of several operant trials must be successfully completed to obtain a reward, monkeys quickly learn to adjust their behavioral performance by using visual cues that signal how many trials have been completed and how many remain in the current schedule. Bilateral rhinal (perirhinal and entorhinal) cortex ablations irreversibly prevent this learning. Here, we apply a recombinant DNA technique to investigate the role of dopamine D2 receptor in rhinal cortex for this type of learning. Rhinal cortex was injected with a DNA construct that significantly decreased D2 receptor ligand binding and temporarily produced the same profound learning deficit seen after ablation. However, unlike after ablation, the D2 receptor-targeted, DNA-treated monkeys recovered cue-related learning after 11-19 weeks. Injecting a DNA construct that decreased N-methyl-d-aspartate but not D2 receptor ligand binding did not interfere with learning associations between the cues and the schedules. A second D2 receptor-targeted DNA treatment administered after either recovery from a first D2 receptor-targeted DNA treatment (one monkey), after N-methyl-d-aspartate receptor-targeted DNA treatment (two monkeys), or after a vector control treatment (one monkey) also induced a learning deficit of similar duration. These results suggest that the D2 receptor in primate rhinal cortex is essential for learning to relate the visual cues to the schedules. The specificity of the receptor manipulation reported here suggests that this approach could be generalized in this or other brain pathways to relate molecular mechanisms to cognitive functions.

Animals↗

PubMed2004

Unilateral deficits in visual perception and learning after unilateral inferotemporal cortex lesions in macaques.

This study adapted the method of partial lesions, combined with controlled fixation, to study the perceptual role of macaque inferotemporal (IT) cortex. Unilateral lesions were made in IT cortex of three monkeys, without section of the corpus callosum, and visual function was tested ipsilateral and contralateral to the lesion. The observed changes were compared to the effects of bilateral lesions of IT cortex in one monkey, the approach used in most previous studies. Unilateral lesions produced far less profound, although more selective, loss on the tested visual abilities than did bilateral lesions. All three monkeys with unilateral lesions showed decreased chromatic sensitivity, but sparing of achromatic sensitivity, and severely disrupted learning and performance of visual matching to sample, and in all cases, the visual loss was contralateral to the site of the lesion. Unexpectedly, the magnitude of the contralateral loss was not increased by later section of the corpus callosum and anterior commissure in one of the monkeys, a lesion that removes interhemispheric input to contralateral from ipsilateral temporal cortex neurons. These results support physiological findings that show that the response of IT cortex neurons is dominated by the contralateral visual field, despite the bilateral activation many IT neurons receive. Comparison to earlier studies of lesions of area V4, which provides input to IT cortex, shows that V4 and IT lesions produce qualitatively different effects.

Animals↗

PubMed2004

Species-specific calls evoke asymmetric activity in the monkey's temporal poles.

It has often been proposed that the vocal calls of monkeys are precursors of human speech, in part because they provide critical information to other members of the species who rely on them for survival and social interactions. Both behavioural and lesion studies suggest that monkeys, like humans, use the auditory system of the left hemisphere preferentially to process vocalizations. To investigate the pattern of neural activity that might underlie this particular form of functional asymmetry in monkeys, we measured local cerebral metabolic activity while the animals listened passively to species-specific calls compared with a variety of other classes of sound. Within the superior temporal gyrus, significantly greater metabolic activity occurred on the left side than on the right, only in the region of the temporal pole and only in response to monkey calls. This functional asymmetry was absent when these regions were separated by forebrain commissurotomy, suggesting that the perception of vocalizations elicits concurrent interhemispheric interactions that focus the auditory processing within a specialized area of one hemisphere.

Acoustic Stimulation↗

PubMed2003

Functional mapping of the primate auditory system.

Cerebral auditory areas were delineated in the awake, passively listening, rhesus monkey by comparing the rates of glucose utilization in an intact hemisphere and in an acoustically isolated contralateral hemisphere of the same animal. The auditory system defined in this way occupied large portions of cerebral tissue, an extent probably second only to that of the visual system. Cortically, the activated areas included the entire superior temporal gyrus and large portions of the parietal, prefrontal, and limbic lobes. Several auditory areas overlapped with previously identified visual areas, suggesting that the auditory system, like the visual system, contains separate pathways for processing stimulus quality, location, and motion.

Acoustic Stimulation↗

PubMed2002

Comparison of hippocampal, amygdala, and perirhinal projections to the nucleus accumbens: combined anterograde and retrograde tracing study in the Macaque brain.

A combination of anterograde and retrograde tracing techniques was used to study the projections to the nucleus accumbens from the amygdala, the hippocampal formation (including the entorhinal cortex), and the perirhinal cortex in two species of macaque monkey. To help identify possible subregions within the nucleus accumbens, the distribution of calbindin was examined in two additional monkeys. Although this revealed evidence of "core"- and "shell"-like regions within the accumbens, these different regions could not consistently be related to cytoarchitectonic features. The rostral amygdala sent nearly equivalent projections to both the medial and the lateral portions of nucleus accumbens, whereas projections arising from the middle and caudal amygdala terminated preferentially in the medial division of nucleus accumbens. The basal nucleus was the major source of these amygdala efferents, and there was a crude topography as parts of the basal and accessory basal nuclei terminated in different parts of nucleus accumbens. The subiculum was the major source of hippocampal projections to the nucleus accumbens, but some hippocampal efferents also originated in the parasubiculum, the prosubiculum, the adjacent portion of CA1, and the uncal portion of CA3. These hippocampal projections, which coursed through the fornix, showed a rostrocaudal gradient as more arose in the rostral hippocampus. Hippocampal efferents terminated most densely in the medial and ventral portions of nucleus accumbens, along with light label in the adjacent olfactory tubercle. The entorhinal projections were more evenly distributed between the medial nucleus accumbens and the olfactory tubercle, whereas the perirhinal projections were primarily to the olfactory tubercle. These cortical inputs were less reliant on the fornix. Amygdala and subicular (hippocampal) projections overlapped most completely in the medial division of nucleus accumbens.

Amygdala↗