Intralaminar Nuclei Research Articles

Monitoring and switching of cortico-basal ganglia loop functions by the thalamo-striatal system.

Recent physiological and tract tracing studies revealed tight coupling of the centre médian and parafascicular nuclei (the CM-Pf complex), which are posterior intralaminar nuclei (ILN) of the thalamus, with basal ganglia circuits. These nuclei have previously been classified as part of the ascending reticulo-thalamo-cortical activating system, with studies of single neuron activity and of interruption of neuronal activity suggested that they participate in the processes of sensory event-driven attention and arousal, particularly in the context of unpredicted events or events contrary to predictions. In this article, we propose a hypothetical model that envisions that the CM-Pf complex functions in two different modes depending on the predictability of external events, i.e., one for monitoring 'top-down' biased control through the cortico-basal ganglia loop system for selecting signals for action and cognition and the other for switching from biased control to 'bottom-up' control based on the signals of salient external events. This model provides a new insight into the function of the CM-Pf complex and should lead to a better understanding of this important brain system.

El tálamo: aspectos neurofuncionales

To carry out a revision of the principal neurofunctional aspects of the thalamus.Following the anatomical location of this cerebral structure in the diencephalon, we'll analyze the macroscopic characteristics of the thalamus establishing its anatomical limits. We'll study the main thalamic nuclei, taking into account different criteria: evolution, anatomical and functional, cytoarchitectonic, and connective fibers as well as the principal projections which reach and leave the thalamus, allowing an adequate information processing. The last part of this paper is dedicated to study of the aspects related with the participation of the thalamus in the basic psychofunctional processes and superior processes.The thalamus, in addition to its implication along with the cerebral cortex in the analysis and integration of sensitive and motor functions, is implied in superior functions like the attention, language, memory and executive function. The pulvinar nucleus, the lateral nuclear group and the anterior nuclear group take part in the language, fundamentally. In the mnesic processes, the scientific studies show that the midline nuclei, mediodorsal thalamic nuclei and intralaminar nuclei of the thalamus are implied in this superior function. Lesions of the thalamus can cause alterations in the executive functions, attention, initiative and temporal organization of the conduct. The mediodorsal nuclei, the intralaminar nuclei and the midline nuclei has been shown to have a critical role in executive function.

Pedunculopontine tegmental nucleus. Part I: cytoarchitecture, transmitters, development and connections

The present review compiles data on the cytoarchitecture, transmitters, development, afferent and efferent connections of the pedunculopontine tegmental nucleus (PPN). PPN is a reticular formation nucleus, located in the pontomesencephalic tegmentum, closely associated with the ascending limb of the superior cerebellar peduncle. Its most typical cells are cholinergic and comprise the Ch5 neuronal group of Mesulam. It contains also glutamatergic neurons that may contain glutamate as a sole transmitter or as a co-transmitter of acetylcholine. The cholinergic neurons use also the gaseous transmitter nitric oxide, being the most prominent nitrergic neurons in the central nervous system (CNS). In aged animals, there is practically no cell loss but there are certain drastic changes in the somatodendritic morphology. PPN has an extremely rich afferent input. All basal ganglia send axons to PPN, the strongest connection being from the substantia nigra (SN), followed by pathways arising from the subthalamic nucleus (STN) and from both pallidal segments (PAL). PPN receives afferents also from the cerebral cortex, from areas of the limbic system and hypothalamus, from the cerebellum, from the brainstem - particularly serotoninergic axons from the raphe nuclei and noradrenergic axons from the locus ceruleus - as well as from the spinal cord. The efferent connections of PPN are extremely diverse, and some of them are carried out by axons that emit divergent collaterals to two different structures. The heaviest efferent pathway of PPN is destined to the thalamus, innervating virtually all thalamic nuclei, and especially the nonspecific intralaminar nuclei, that innervate broad ares of the cerebral cortex. All basal ganglia are innervated and in most cases the connection is bilateral. The most significant pathway innervates the dopaminergic neurons of SN, followed by a connection to STN and PAL. Other PPN efferent connections reach the cerebellum, the superior colliculus, nuclei of cranial nerves, the reticular formation, and the spinal cord. The reviewed connections of PPN suggest that it is involved significantly in the arousal systems, and is implicated in the disturbances of sleep and wakefulness. PPN is also involved in the motor functions of CNS, as well as in the movement disorders. Biomedical Reviews 2003; 14: 95-120.

Organization of axonal projections from the anterolateral area of the bed nuclei of the stria terminalis.

The anterolateral group of the bed nuclei of the stria terminalis (BSTalg) contains four distinct cell groups embedded within an undifferentiated anterolateral area (BSTal) that architectonically resembles a subjacent subcommissural zone (BSTsc). The overall distributions of axonal projections from various regions of the BSTal and from the BSTsc were determined with the Phaseolus vulgaris-leucoagglutinin (PHAL) anterograde tracer method and found to be identical. The BSTal and BSTsc share dense bidirectional connections, and also project heavily within the BST to the rhomboid and fusiform nuclei and the anteroventral and anterodorsal areas. They project less densely to the juxtacapsular, oval, magnocellular, ventral, and interfascicular BST nuclei. Outside the BST, brain areas receiving strong to moderate inputs from the BSTal and BSTsc fall into several functional groups: somatomotor system (nucleus accumbens, substantia innominata, ventral tegmental area, and retrorubral area and adjacent midbrain reticular nucleus), central autonomic control system (central amygdalar nucleus, dorsal lateral hypothalamic area, ventrolateral periaqueductal gray, parabrachial nucleus, and nucleus of the solitary tract), neuroendocrine system (paraventricular and supraoptic nuclei, hypothalamic visceromotor pattern generator network), and thalamocortical feedback loops (midline, medial, and intralaminar nuclei). The results indicate that the BSTal and BSTsc are parts of the same cell group (dorsal and ventral to the anterior commissure), which plays a role in coordinating visceral and somatic motor responses (during ingestive behaviors, for example), especially in response to noxious stimuli (learned anorexia associated with noxious stimuli). BSTal projections are distinct from those of the adjacent juxtacapsular, oval, fusiform, and rhomboid nuclei.

Input–output organization of the rostral part of the dorsal premotor cortex, with special reference to its corticostriatal projection

Until recently, little was known about the rostral part of the dorsal premotor cortex (PMdr). In the present study, somatotopical representations of the PMdr were electrophysiologically identified in the macaque monkey, and the distribution of corticostriatal input from the forelimb region of the PMdr was analyzed in relation to its thalamocortical and intracortical (with the frontal lobe) connections. Results have revealed that (1) the forelimb is represented predominantly in the PMdr, while only a few sites representing other body parts are distributed as embedded within the forelimb representation; (2) the corticostriatal input zone is located in the striatal cell bridges and their surroundings; (3) the cells of origin of the thalamocortical projections to the PMdr are located mainly in the parvicellular division of the ventroanterior nucleus, the oral divison of the ventrolateral nucleus, area X, the caudal divison of the ventrolateral nucleus, the mediodorsal nucleus, and the intralaminar nuclear group; (4) the PMdr is interconnected primarily with higher-order motor-related areas and dorsal area 46. These data indicate that the input–output pattern of the PMdr resembles those of the presupplementary motor area and the rostral cingulate motor area, and that the PMdr may play critical roles in higher-order motor functions.

Brain Activation during Human Male Ejaculation

Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation in heterosexual male volunteers. Manual penile stimulation was performed by the volunteer's female partner. Primary activation was found in the mesodiencephalic transition zone, including the ventral tegmental area, which is involved in a wide variety of rewarding behaviors. Parallels are drawn between ejaculation and heroin rush. Other activated mesodiencephalic structures are the midbrain lateral central tegmental field, zona incerta, subparafascicular nucleus, and the ventroposterior, midline, and intralaminar thalamic nuclei. Increased activation was also present in the lateral putamen and adjoining parts of the claustrum. Neocortical activity was only found in Brodmann areas 7/40, 18, 21, 23, and 47, exclusively on the right side. On the basis of studies in rodents, the medial preoptic area, bed nucleus of the stria terminalis, and amygdala are thought to be involved in ejaculation, but increased rCBF was not found in any of these regions. Conversely, in the amygdala and adjacent entorhinal cortex, a decrease in activation was observed. Remarkably strong rCBF increases were observed in the cerebellum. These findings corroborate the recent notion that the cerebellum plays an important role in emotional processing. The present study for the first time provides insight into which regions in the human brain play a primary role in ejaculation, and the results might have important implications for our understanding of how human ejaculation is brought about, and for our ability to improve sexual function and satisfaction in men.

Organization of cortico-hippocampal networks in rats related to learning and memory

Declarative memory is largely mediated by neuronal networks in the medial temporal lobe/(para)hippocampal system, whereas executive functions and attention strongly depend on the circuitry of the prefrontal lobe. There is convincing evidence that the two cortical systems function as complementary systems in normal cognition, including learning and memory, and that disruption of the interplay between the two lead to profound deficits. On the basis of our own experimental anatomical data in the rat, we suggest that this interplay is mediated by at least three direct and indirect parallel pathways. The first one makes use of direct projections from the hippocampal formation to the prefrontal cortex (PFC), as well as parallel indirect routes through the parahippocampal region. The second pathway comprises the connections of both domains with intrinsically connected parts of the posterior and anterior cingular cortices. Finally, the strong and rather specific reciprocal connections with certain midline and intralaminar thalamic nuclei form a third pathway for hippocampal–prefrontal systems to interact. Lesions disrupting any of these three routes lead to specific learning and memory deficits both in experimental animals as well as in humans, supporting the functional relevance of each of these pathways.

Vascular syndromes of the thalamus.

This article reviews the anatomy, connections, and functions of the thalamic nuclei, their vascular supply, and the clinical syndromes that result from thalamic infarction. Thalamic nuclei are composed of 5 major functional classes: reticular and intralaminar nuclei that subserve arousal and nociception; sensory nuclei in all major domains; effector nuclei concerned with motor function and aspects of language; associative nuclei that participate in high-level cognitive functions; and limbic nuclei concerned with mood and motivation. Vascular lesions destroy these nuclei in different combinations and produce sensorimotor and behavioral syndromes depending on which nuclei are involved. Tuberothalamic territory strokes produce impairments of arousal and orientation, learning and memory, personality, and executive function; superimposition of temporally unrelated information; and emotional facial paresis. Paramedian infarcts cause decreased arousal, particularly if the lesion is bilateral, and impaired learning and memory. Autobiographical memory impairment and executive failure result from lesions in either of these vascular territories. Language deficits result from left paramedian lesions and from left tuberothalamic lesions that include the ventrolateral nucleus. Right thalamic lesions in both these vascular territories produce visual-spatial deficits, including hemispatial neglect. Inferolateral territory strokes produce contralateral hemisensory loss, hemiparesis and hemiataxia, and pain syndromes that are more common after right thalamic lesions. Posterior choroidal lesions result in visual field deficits, variable sensory loss, weakness, dystonia, tremors, and occasionally amnesia and language impairment. These vascular syndromes reflect the reciprocal cerebral cortical-thalamic connections that have been interrupted and provide insights into the functional properties of the thalamus.

Anatomical organization of the telencephalic connections of the parafascicular nucleus in adult and developing rats

The parafascicular nucleus (PFN) of the rat, homologous to the human centre médian, is an intralaminar nucleus of the thalamus, classically considered as part of the ascending activating system. We have previously demonstrated that it is also connected to several subcortical nuclei. To obtain a more detailed picture of the connectivity of the PFN, the organization and the topography of the reciprocal parafascicular-telencephalic relationships were studied in both adult and developing rats, using anterograde and retrograde neuronal tracers. In the adult rat, the ascending parafascicular projections were densest to the striatum, dense to the frontal and least dense to cingulate cortex, and were strictly ipsilateral. They displayed a loose topography, with the more medial parafascicular neurons projecting to the medial frontal and cingulate cortex and medial striatum, and the more lateral neurons projecting to the lateral frontal cortex and lateral striatum. All these connections were already present at embryonic day 19. Parafascicular neurons projecting to the telencephalon in adult rats were mostly of the multipolar type, with a few bipolar neurons. In neonatal rats they showed a bipolar morphology at birth; they became mostly multipolar later on, with an increasing complexity of the dendritic arbor up to postnatal day 10. Neurons in the frontal cortex retrogradely labelled from the PFN were more numerous perinatally, and decreased as early as postnatal day 5. The telencephalic connections of the PFN were found to be more discrete and restricted than previously thought, thus suggesting a more specific functional role for the nucleus than cortical recruitment.

Parvocellular subparafascicular thalamic nucleus in the rat: anatomical and functional compartmentalization.

The parvocellular subparafascicular thalamic nucleus (SPFp) is located in the posterior thalamus, consists of horizontally oriented cells, and extends from rostromedial to caudolateral, fusing with the posterior intralaminar nucleus and the peripeduncular nucleus. The present study demonstrates a chemoarchitechtonic and functional parcellation of the rat SPFp. Analysis of the distributions of the neuropeptides galanin, calcitonin gene related peptide (CGRP), substance P, and calbindin revealed the existence of a medial and lateral subdivision within SPFp, and a possible intermediate subdivision. The medial subdivision contains a dense population of galanin-immunoreactive fibers, originating from galanin neurons in the lumbosacral spinal cord. In contrast, the lateral subdivision contains CGRP-positive fibers and neurons. The presence of substance P and calbindin immunoreactivity throughout the entire nucleus suggests that these are separate subdivisions of SPFp, rather than different subnuclei. The present study also investigated the functional association of the separate subdivisions of SPFp for male and female rat sexual behavior. In the medial subdivision, Fos-positive neurons were activated in males by display of ejaculation and in females by vaginocervical stimulation. Thus, Fos induction in medial SPFp appears to reflect processing of inputs related to those events. In contrast, sexual behavior did not induce Fos in the lateral SPFp. Taken together, the present results indicate the existence of separate subdivisions in SPFp that are involved in different behavioral functions. The medial SPFp may process inputs important for sexual behavior, whereas the lateral SPFp may be involved in convergence of auditory and nociceptive inputs important for conditioned fear responses.

Differential distribution of butyrylcholinesterase and acetylcholinesterase in the human thalamus.

It has been hypothesized that acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are coregulators of the duration of action of acetylcholine in cholinergic neurotransmission, suggesting that BuChE may also have an important role in the brain. To compare the expression of cholinesterases in the human thalamus, the distributions of BuChE and AChE activity were studied by using a modified Karnovsky-Roots method. BuChE activity was present mainly in neurons, whereas AChE activity was present in both neurons and axons. There was intense staining for BuChE or AChE throughout the thalamus, with some nuclei primarily expressing one or the other cholinesterase. BuChE staining was most intense and widespread in neurons in the anteroventral, mediodorsal, ventral, lateral, and pulvinar thalamic nuclei. AChE was predominantly expressed in neurons of the anterodorsal, midline, ventral, intralaminar, and reticular nuclei. Many nuclei contained both cholinesterases. Considering the overall patterns of labeling in the thalamus for the two cholinesterases, there were both complementary and overlapping relationships of BuChE and AChE activity. Neuronal staining in the subthalamic nucleus and hypothalamus was predominantly positive for AChE activity. The distinct distribution of BuChE activity in neurons in the human thalamus is consistent with an important role for this enzyme in neurotransmission in the human nervous system. Furthermore, BuChE activity, like AChE activity, is found in certain thalamic nuclei related to cognitive and behavioral functions. Involvement of thalamic nuclei in diseases of the nervous system such as Alzheimer's disease and schizophrenia suggests that BuChE could be a potential target for therapeutic intervention in these disorders.

Distribution of ORL-1 receptor binding and receptor-activated G-proteins in rat forebrain and their experimental localization in anterior cingulate cortex

Opioid receptor-like (ORL-1) receptors and ORL-1-activated G-proteins are found in high levels in the forebrain, particularly cingulate cortex, an area involved in processing of nociceptive stimuli. [ 3H]nociceptin/orphanin FQ (N/OFQ) and N/OFQ-stimulated [ 35S]GTPγS autoradiography in rat brain were used to localize ORL-1 receptors and activated G-proteins, respectively. N/OFQ binding and activated G-proteins were highest in anterior cingulate, agranular insula, piriform, perirhinal and entorhinal cortices; midline and intralaminar thalamic nuclei; and subnuclei of the amygdala and hippocampus. In anterior cingulate area 24, [ 3H]N/OFQ and N/OFQ-stimulated [ 35S]GTPγS binding were highest in layers V and VI. The cellular localization of ORL-1 receptors and activated G-proteins in area 24 was examined using two strategies: ibotenic acid injection into the cortex or undercut lesions to remove afferent axons, followed by autoradiography. Ibotenic acid lesions that destroyed neurons in the anterior cingulate cortex decreased [ 3H]N/OFQ binding by 75–80% and reduced N/OFQ-stimulated [ 35S]GTPγS binding to basal levels seen in the absence of agonist. Deafferentation lesions increased [ 3H]N/OFQ binding by 40–50%, with no significant change in N/OFQ-stimulated [ 35S]GTPγS binding. These data demonstrate that ORL-1 receptors in layer V of anterior cingulate cortex are located on somatodendritic elements and that deafferentation increases ORL-1 receptor binding.

Thalamocortical and intracortical connections of monkey cingulate motor areas.

Although there has been an increasing interest in motor functions of the cingulate motor areas, data concerning their input organization are still limited. To address this issue, the patterns of thalamic and cortical inputs to the rostral (CMAr), dorsal (CMAd), and ventral (CMAv) cingulate motor areas were investigated in the macaque monkey. Tracer injections were made into identified forelimb representations of these areas, and the distributions of retrogradely labeled neurons were analyzed in the thalamus and the frontal cortex. The cells of origin of thalamocortical projections to the CMAr were located mainly in the parvicellular division of the ventroanterior nucleus and the oral division of the ventrolateral nucleus (VLo). On the other hand, the thalamocortical neurons to the CMAd/CMAv were distributed predominantly in the VLo and the oral division of the ventroposterolateral nucleus-the caudal division of the ventrolateral nucleus. Additionally, many neurons in the intralaminar nuclear group were seen to project to the cingulate motor areas. Except for their well-developed interconnections, the corticocortical projections to the CMAr and CMAd/CMAv were also distinctively preferential. Major inputs to the CMAr arose from the presupplementary motor area and the dorsal premotor cortex, whereas inputs to the CMAd/CMAv originated not only from these areas but also from the supplementary motor area and the primary motor cortex. The present results indicate that the CMAr and the caudal cingulate motor area (involving both the CMAd and the CMAv) are characterized by distinct patterns of thalamocortical and intracortical connections, reflecting their functional differences.

The associative striatum: cortical and thalamic projections to the dorsocentral striatum in rats

Corticostriatal projections to the dorsocentral striatum (DCS) were investigated using retrograde fluorescent axonal tracing. The DCS is of interest because of its role in directed attention and recovery from multimodal hemispatial neglect following cortical lesions of medial agranular cortex (AGm), an association area that is its major source of cortical input. A key finding was that the multimodal posterior parietal cortex (PPC) also contributes substantial input to DCS. This is significant because PPC and AGm are linked by corticocortical connections and are both critical components of the circuitry involved in spatial processing and directed attention. Other cortical areas providing input to DCS include visual association areas, lateral agranular cortex and orbital cortex. These areas also have reciprocal connections with AGm and PPC. Less consistent labeling was seen in somatic sensorimotor areas FL, HL and Par 1. Thalamic afferents to DCS are prominent from the intralaminar, ventrolateral, mediodorsal, ventromedial, laterodorsal (LD) and lateral posterior (LP) nuclei. Collectively, these nuclei constitute the sources of thalamic input to cortical areas AGm and PPC. Nuclei LD and LP are only labeled with injections in dorsal DCS, the site of major input from PPC, and PPC receives its thalamic input from LD and LP. We conclude that DCS receives inputs from cortical and thalamic areas that are themselves linked by corticocortical and thalamocortical connections. These findings support the hypothesis that DCS is a key component of an associative network of cortical, striatal and thalamic regions involved in multimodal processing and directed attention.

Contributions of Thalamic Nuclei to Declarative Memory Functioning

In spite of the acknowledged role that the thalamus plays in declarative memory, details about the precise memory processes it is involved in and which are the structures of the thalamus that contribute to these processes remain unknown. An overview is presented of human clinical and animal experimental findings showing the involvement of the thalamus, at the level of white matter tracts and separate nuclei, in aspects of memory functioning. The region in the thalamus that contributes to declarative memory is the anterior and medial division, containing the anterior nuclei, the medial dorsal nucleus and the intralaminar and midline nuclei. A lesion to the anterior nuclei or their afferent white matter tract, the mammillothalamic tract, results in deficits of encoding of new stimuli. Lesions to the medial dorsal nucleus affect executive processes pertaining to declarative memory, such as the use of memory strategies for retrieval; damage to the intralaminar and midline nuclei results in decreased arousal and thus affects the declarative memory process. Based on anatomical and functional data, a theory is proposed of how the thalamus might play a role at different levels of declarative memory functioning. Firstly, the anterior and mediodorsal nucleus are involved in processing the contents of the stimuli for storage and recall. The anterior nuclei influence the selection of material to be stored and remembered, whereas the mediodorsal nucleus is involved in the coordination and selection of the strategies used to retrieve material. Secondly, the intralaminar and midline nuclei and specifically the lateral and ventral components, maintain a necessary state of the cortical regions involved in the ongoing memory processes. The two types of function subserved by these groups of thalamic nuclei, focussing on contents vs. state, need to work in parallel to mediate and allow memory functioning, respectively.

Deficits of memory, executive functioning and attention following infarction in the thalamus; a study of 22 cases with localised lesions

The thalamus plays a crucial role in memory, executive functioning and attention. It remains, however, unclear whether thalamic structures have specific roles in each of these functions. We tested 22 cases of thalamic infarction, proven with MR imaging, using experimental and established neuropsychological tests. We performed a lesion-overlap study in standardised stereotactic space of patients sharing a certain deficit, corrected for the lesion distribution of patients without such deficits and determined the regions of interest using an atlas of the human thalamus. We checked for additional, non-thalamic, damage and for deficient comprehension and perception that would preclude interpretation of the results. Non-thalamic damage such as white matter lesions, hippocampal atrophy, sulcal widening and infarctions occur significantly more often in patients aged over 60. The patients with additional damage overlapped to a major degree with those who showed loss of orientation, or lack of comprehension of the test requirements. In the 10 patients judged ‘clean’, we observed a deficit of episodic long-term memory with relative sparing of intellectual capacities and short-term memory when the mammillo-thalamic tract was damaged. Lesions including the medial dorsal nucleus, midline nuclei and/or intralaminar nuclei accompany executive dysfunctioning. Reduced simple processing speed and attention are associated with age, but not with a particular structure in the thalamus. Complex attention deficits follow damage to the intralaminar nuclei. We conclude that the analysis of structure–function relationships must take into account extra-structure damage which may explain cognitive deficits. Separate thalamic structures are involved in memory, executive functioning and attention.

Expression and distribution of tuberoinfundibular peptide of 39 residues in the rat central nervous system.

Tuberoinfundibular peptide of 39 residues (TIP39) has been recently purified and identified as a selective ligand for the parathyroid hormone 2 receptor. As a next step toward understanding its functions, we report the expression and distribution of TIP39 in the rat central nervous system. In situ hybridization histochemistry and immunocytochemistry revealed TIP39-containing cell bodies in three distinct areas. The major one comprises the subparafascicular area posterior through the intralaminar nucleus of the thalamus; a second is the medial paralemniscal nucleus at the pontomesencephalic junction; and a third is in the dorsal and dorsolateral hypothalamic areas, which contained a few, scattered cell bodies. We found, in contrast to the highly restricted localization of TIP39-containing cell bodies, a much more widespread localization of TIP39-containing fibers. The highest density of fibers was observed in limbic areas such as the septum, the amygdala, and the bed nucleus of the stria terminalis; in areas involved in endocrine regulation, such as the hypothalamic dorsomedial, paraventricular, periventricular, and arcuate nuclei; in auditory areas, such as the ectorhinal and temporal cortices, inferior colliculus, medial geniculate body, and some of the nuclei of the superior olivary complex; and in the dorsolateral funiculus of the spinal cord. The localization of TIP39-containing nuclei and fibers provides an anatomical basis for previously demonstrated endocrine and nociceptive effects of TIP39 and suggests additional functions for TIP39, one apparent candidate being the regulation of auditory information processing.

The efferent connections of the pupillary constriction area in the rat medial frontal cortex

This study investigated, in the rat, the efferent projections of the pupillary constriction area, which is located within the medial frontal cortex. In order to identify the location of the pupillary constriction area, in preliminary experiments the medial frontal cortex was microstimulated. Intracortical microstimulation elicited pupillary constriction in a thin strip of cortex near the interhemispheric fissure and bordering the frontal eye field and vibrissae area of the somatomotor cortex. Seven animals received a single iontophoretic injection of Phaseolus vulgaris leucoagglutinin in the pupillary constriction area. In these cases, anterogradely labelled fibres and terminal-like elements were found in both hemispheres. The densest labeling was seen in several areas of the injected hemisphere, where labeled fibers prevailed in the secondary visual cortex. Dense labeled fibers were also found in the retrosplenial and cingulate cortex. In the thalamus, labeled fibers were seen in the intralaminar nuclei and posterior nuclear group. In the midbrain and pons, labeled fibers were located in the anterior pretectal area, superior colliculus and in the dorsolateral portion of the central gray. Contralaterally to the injection site, labeled fibers were distributed in the homotopic region. These findings led us to assume that, in the medial frontal cortex of the rat, besides controlling pupillary constriction, the pupillary constriction area may also be involved in controlling orientation and exploring behavior.

Towards a neurophysiological foundation for cognitive neuromodulation through deep brain stimulation

It may soon be possible to adapt the use of deep brain stimulation (DBS) technologies developed to treat movement disorders to improve the general cognitive function of brain-injured patients. We outline neurophysiological foundations for novel neuromodulation strategies to address these goals. Emphasis is placed on developing a rationale for targeting the intralaminar and related nuclei of the human thalamus for electrical stimulation. Recent anatomical and physiological studies are compared with original neurophysiological recordings obtained in an alert non-human primate. In this context we consider neuronal mechanisms that may underlie both clinical observations and cognitive rehabilitation maneuvers that provide theoretical support for open and closed-loop strategies to remediate acquired cognitive disability (ACD).

New Intrathalamic Pathways Allowing Modality-Related and Cross-Modality Switching in the Dorsal Thalamus

Transmission through the dorsal thalamus involves nuclei that convey different aspects of sensory or motor information. Cells in the dorsal thalamus are strongly inhibited by the GABAergic cells of the thalamic reticular nucleus (TRN). Here we show that stimulation of cells in specific dorsal thalamic nuclei evokes robust IPSCs or IPSPs in other specific dorsal thalamic nuclei and vice versa. These IPSCs are GABA(A) receptor-mediated currents and are consistent with the activation of disynaptic intrathalamic pathways mediated by TRN. Thus, cells engaged in sensory analyses in the ventrobasal complex or the medial division of the posterior complex can interact with cells responsive to sensory events in the caudal intralaminar nuclei, whereas cells engaged in motor analyses in the ventrolateral nucleus can interact with cells responsive to motor events in the rostral intralaminar nuclei. Furthermore, sensory event-related cells in the caudal intralaminar nuclei can interact with motor event-related cells in the rostral intralaminar nuclei. In addition, single cells in one dorsal thalamic nucleus can receive convergent inhibitory inputs after stimulation of cells in two or more other dorsal thalamic nuclei, and TRN-mediated inhibitory inputs can momentarily switch off tonic firing of action potentials in dorsal thalamic cells. Our findings provide the first direct evidence for a rich network of intrathalamic pathways that allows modality-related and cross-modality inhibitory modulation between dorsal thalamic nuclei. Moreover, TRN-mediated switching between dorsal thalamic nuclei could provide a mechanism for the selection of competing transmissions of sensory and/or motor information through the dorsal thalamus.