Research Article
Neurofilament subunit protein abnormalities in the thalamus in schizophrenia
- Sarah M. Clinton, Sara Abelson, Vahram Haroutunian, Kenneth Davis, James H. Meador-Woodruff
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- 18 April 2006, pp. 265-272
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Postmortem and in vivo imaging studies have revealed structural and functional pathology in the thalamus in schizophrenia. We have reported a series neurochemical changes in the thalamus in schizophrenia, including decreased expression of NMDA receptor subunit transcripts and increased levels of NMDA receptor-associated intracellular proteins like postsynaptic density protein 95 (PSD95) and neurofilament-light (NF-L) chain that link the NMDA receptor to downstream signal transduction pathways. NF-L, along with the neurofilament subunit proteins NF-medium (NF-M) chain and NF-heavy (NF-H) chain, assemble to form neurofilaments, one of the most abundant cytoskeletal elements. While the neurofilament subunits play a crucial role in sustaining the neuronal cytoskeleton, two subunits, NF-L and NF-M, also participate in neurotransmission, interacting with the NMDA and the dopamine Dl receptors, respectively. In the present study, using in situ hybridization, we determined whether all of the neurofilament subunits (NF-L, NF-M, and NF-H) are abnormally expressed in the thalamus in schizophrenia, or whether the abnormality is specific to NF-L. We found that NF-L and NF-M transcripts are both increased in schizophrenia, but the expression of NF-H is unchanged. Both NF-L and NF-M play an important role in maintaining the neuronal cytoskeleton, so abnormal transcript expression may be associated with structural thalamic pathology. Alternatively, since these proteins are also known to interact with the NMDA and Dl dopamine receptors, abnormal transcript levels may be associated with abnormalities of neurotransmission in the thalamus in schizophrenia.
Subthalamic nucleus: a clock inside basal ganglia?
- C. Beurrier, L. Garcia, B. Bioulac, C. Hammond
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- 18 April 2006, pp. 1-8
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Subthalamic nucleus (STN) neurons have a pivotal role in basal ganglia, as a result of their intrinsic membrane properties, connections within the circuit and glutamatergic nature. Their innate pacemaker activity, consisting of a single-spike tonic mode of discharge, is abolished in the case of hemiballism, profoundly disrupted in the Parkinsonian state and replaced by a regular bursting mode under treatment (high-frequency stimulation, HFS). We propose that control STN activity represents a clock, an internal measure of time allowing the correct automatic execution of learned movements and, in particular, the automatic switch from one movement to the next in a sequential motor pattern. STN neuronal activity would be able to reset the frequency of oscillations of motor thalamo-cortical loops, notably in the γ band.
Ascending inputs to the pre-supplementary motor area in the macaque monkey: cerebello- and pallido-thalamocortical projections
- Sharleen T. Sakai, Iwona Stepniewska, Huixin Qi, Jon H. Kaas
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- 18 April 2006, pp. 175-187
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The goal of the present study was to determine the ascending sources to the pre-supplementary motor area (pre-SMA) in macaque monkeys using multiple labeling techniques. We labeled the pallidothalamic projections using biotinylated dextran amine (BDA) and the cerebellothalamic projections using wheatgerm agglutinin conjugated to horseradish peroxidase. The pre-SMA thalamocortical projections neurons were also labeled using cholera toxin subunit b following identification of the pre-SMA by location, and by movements evoked by intracortical microstimulation. The extent of pre-SMA was later confirmed by identifying characteristics from Nissl cytoarchitecture and SMI-32 immunoreactivity. Thalamic nuclear boundaries were based on Nissl cytoarchitecture, acetylcholinesterase chemoarchitecture and Cat-301 immunoreactivity. Cerebellothalamic afferents were distributed predominantly to ventral lateral posterior nucleus (VLp), including medial and dorsal VLp, while the pallidothalamic afferents projected more rostrally to ventral lateral anterior nucleus (VLa) and ventral anterior nucleus (VA). The pre-SMA thalamocortical projection neurons were primarily found in VA and medial VLp. However, scattered cells were also found in VLa, dorsal VLp, central lateral nucleus (CL) and mediodorsal nucleus (MD). Scattered pre-SMA projecting cells overlapped foci of cerebellar label in medial VLp. Additionally, limited overlap of pre-SMA cells and pallidothalamic labeling was found in caudal VA. These findings suggest that the pre-SMA is uniquely positioned to integrate ascending basal ganglia and cerebellar information after a relay from VA and medial VLp. These anatomical findings are consistent with the recent hypothesis that the pre-SMA acts as the coordinator of visual and motor loops in motor learning [J. Cogn. Neurosci. 13 (2001) 626].
Editorial
Editor in Chief's Perspective
- M. Steriade
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- 18 April 2006, p. 93
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Research Article
The dual pattern of corticothalamic projection of the premotor cortex in macaque monkeys
- Eric M. Rouiller, Thierry Wannier, Anne Morel
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- 18 April 2006, pp. 189-197
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The terminals formed by the corticothalamic axons are of two types, small and giant endings. This dual mode of corticothalamic projection has been found to be consistent across species (mouse, rat, cat, monkey) and across systems (visual, auditory, somatosensory and motor). In the monkey, this dual mode of projection has been demonstrated for the motor system in the case of the primary motor cortical area, the supplementary motor area and the caudal part of the dorsal premotor cortex. Based on biotinylated dextran amine anterograde tracing experiments, a similar dual mode of termination morphology was found here for corticothalamic axons originating from the other three distinct sub-divisions of the premotor cortex. Furthermore, the pattern of arrangement of giant endings originating from the premotor cortex was found to be similar to that from the supplementary motor area but different to that from the primary motor cortex.
Might deep brain stimulation of the subthalamic nucleus be neuroprotective in patients with Parkinson’s disease?
- Alim Louis Benabid, Brigitte Piallat, Bradley Wallace, Abdelhamid Benazzouz, Doris Lenartz, Christian Andressen, Paul Krack, Pierre Pollak
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- 18 April 2006, pp. 95-102
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Parkinson’s disease (PD) is characterized by nigral degeneration of dopaminergic neurons in the pars compacta of the substantia nigra. Rather than treating only the symptomatic aspects of Parkinson’s disease, one may also consider treatments designed to retard, arrest, or even reverse this degenerative process. Such strategies could include preventive or restorative treatments instead of purely palliative treatments. A recent hypothesis states that glutamate output from the subthalamic nucleus (STN) to the substantia nigra contributes to the neurotoxic process underlying dopaminergic cell death in Parkinson’s disease. Furthermore, high-frequency stimulation (HFS) of the STN inhibits neurons resulting in the suppression of their glutamate output. Experiments in both rats and monkeys provide preliminary data supporting this hypothesis. Kainic acid (KA) lesions of the STN prevent the loss of dopaminergic neurons in the substantia nigra after intrastriatal injection of 6-hydroxydopamine (6-OHDA) in rats, and after systemic administration of MPTP in monkeys. In PD patients, the background level of their disease is evaluated in the off medication/off stimulation state (UPDRS III score), over a period of 5 years. Thirty percent of the patients are stabilized and 18% have persistent improvement of their disease-related impairment. Further experiments are needed, including controlled clinical trials utilizing functional imaging of the dopamine transporters and post-synaptic receptors.
Pallidothalamocortical pathway to the medial agranular cortex in the rat: a double labeling light and electron microscopic study
- Sharleen T. Sakai, Kathy Bruce
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- 18 April 2006, pp. 273-286
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The goal of the present study was to determine if the medial agranular cortex (AGm) that is thought to contain the supplementary motor area in the rat receives the pallidothalamocortical pathway. A double labeling paradigm was employed whereby injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the entopeduncular nucleus (EN) were combined with injections of the retrograde tracer cholera toxin subunit B into either the rostral or caudal part AGm in the rat. We found that the pallidothalamic projections occupied a crescent shaped arc within the thalamic ventral anterior-ventral lateral nuclear complex (VAL) and ventral medial nucleus (VM). Additional efferents projected to LD/LP, MD, Pf and CL. Dense projections were also found to LHb. In addition, we found that a wide band of cells extending from rostral thalamus including VAL and VM through caudal thalamus including MD, Po, LD/LP, Pf and CL projected to either the rostral or caudal parts of the AGm. The greatest coincidence of the pallidothalamic efferents and AGm thalamocortical cells was found in VAL and VM where numerous PHA-L varicosities were found in close apposition to CTB labeled cells. Synaptic contacts between VAL thalamocortical neurons and pallidal terminals were verified in the electron microscope. These results demonstrate for the first time the pallidothalamocortical pathway by way of VAL to the AGm in the rat.
The sleep state-dependent midlatency auditory evoked P50 potential in various disorders
- E. Garcia-Rill, R.D. Skinner, J. Clothier, J. Dornhoffer, E. Uc, A. Fann, N. Mamiya
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- 18 April 2006, pp. 9-19
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The P50 potential is a midlatency auditory evoked response which is sleep state-dependent, habituates rapidly and is blocked by the muscarinic cholinergic antagonist scopolamine. It is thought to be generated, at least in part, by ascending projections of the reticular activating system. The amplitude of the P50 potential can be used as a measure of level of arousal, while the degree of habituation to repetitive stimulation can be used as a measure of sensory gating. We studied these processes in three conditions which show sleep-wake cycle dysregulation and attentional disturbance, but differ greatly in their etiology, depression, Huntington’s disease and rotation-induced motion sickness. Subjects with depression and rotation-induced motion sickness showed significant decreases in the habituation of the second of paired evoked responses, while Huntington’s disease subjects showed decreased amplitude as well as decreases in the habituation of the second P50 potential. This waveform may represent the manifestation of pre-attentional processes, and may become a useful measure for monitoring the severity, progression and/or remission of disorders which affect these processes.
Neural basis of alertness and cognitive performance impairments during sleepiness II. Effects of 48 and 72 h of sleep deprivation on waking human regional brain activity
- Maria L. Thomas, Helen C. Sing, Gregory Belenky, Henry H. Holcomb, Helen S. Mayberg, Robert F. Dannals, Henry N. Wagner Jr., David R. Thorne, Kathryn A. Popp, Laura M. Rowland, Amy B. Welsh, Sharon M. Balwinski, Daniel P. Redmond
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- 18 April 2006, pp. 199-229
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Sleep deprivation impairs alertness and cognitive performance, and these deficits suggest decreases in brain activity and function, particularly in the prefrontal cortex, a region subserving alertness, attention, and higher-order cognitive processes and in the thalamus, a subcortical structure involved in alertness and attention. To substantiate this premise, we characterized the effects of 24, 48, and 72 h of progressive sleep deprivation on brain activity by assessing regional cerebral metabolic rate for glucose (CMRglu) during complex cognitive task performance in 17 young, normal, healthy male volunteers using positron emission tomography (PET) and l8Fluoro-2-deoxyglucose (18FDG). The results of prolonged sleep deprivation, 48 and 72 h, are reported here. Compared to rested baseline (RB), global CMRglu decreased by 6% at 48 and 72 h sleep deprivation (SD) and approximated the 8% decrease seen at 24 h SD. Absolute and relative regional CMRglu decreased at 48 and 72 h SD primarily in the prefrontal and parietal cortices and in the thalamus, the same areas that showed decreases at 24 h SD. Compared to 24 h SD, relative regional CMRglu decreased further in the prefrontal cortex and dorsal thalamus at 48 and 72 h, and at 72 h SD in a limited area of medial visual cortex. Relative regional CMRglu increased in lateral superior occipital cortices, lingual and fusiform gyri, anterior cerebellum, and in primary and supplementary motor cortices at 48 and 72 h SD, indicating a rebound CMRglu activity response from 24 h SD. Polysomnographic monitoring confirmed that subjects were awake. Behavioral outcomes showed continuing decreases in alertness, cognitive performance, and saccadic velocity (a measure of oculomotor response) with prolonged sleep deprivation. Progressive decreases in relative CMRglu values in prefrontal, thalamic, and primary visual areas were correlated positively with the impairments in cognitive performance and saccadic velocity across the 72 h sleep deprivation period. Relative thalamic activity was also correlated with the alterations in alertness. The prefrontal and thalamic regions were positively correlated, suggesting that sleep deprivation impacted these areas together as a functional network.
We propose that the decreases in CMRglu induced in the prefrontal-thalamic network by prolonged sleep deprivation underlie the decline in alertness and cognitive performance and signify the brain’s involuntary progression toward sleep onset, while the increases in visual and motor areas express the brain’s exertion of voluntary control to remain awake and perform. This exertion of voluntary control is manifest in increased subject effort and physical movement, and the recruitment of additional brain regions may reflect an attempt to sustain alertness and cognitive performance despite a continuing decline in prefrontal-thalamic activity. Our findings provide support for the notion of a specific sensitivity of the prefrontal cortex to, and a pivotal role of the thalamus in, sleepiness.
Neuropsychiatric thalamocortical dysrhythmia: surgical implications
- D. Jeanmonod, J. Schulman, R. Ramirez, R. Cancro, M. Lanz, A. Morel, M. Magnin, M. Siegemund, E. Kronberg, U. Ribary, M. Llinas
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- 18 April 2006, pp. 103-113
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Neuropsychiatric surgery has had a long and complex history with examples of less than optimal surgical procedures implemented in wrong settings. Such past errors have raised important philosophical and ethical issues that remain with us for good reasons. However, the existence of enormous suffering due to chronic therapy-resistant disabling neuropsychiatric disorders compels a search for alternative surgical approaches based on a sound understanding of the underlying physiopathological mechanisms. We bring evidence, from single cell physiology and magnetoencephalography, for the existence of a set of neuropsychiatric disorders characterized by localized and protracted low frequency spontaneous recurrent activation of the thalamocortical system. This condition, labeled thalamocortical dysrhythmia, underlies certain chronic psychotic, affective, obsessive compulsive, anxiety and impulse control disorders. Considering the central role of recurrent oscillatory thalamocortical properties in the generation of normal hemispheric functions, we propose a surgical approach that provides a reestablishment of normal thalamocortical oscillations without reduction of cortical tissue and its specific thalamic connectivity. It consists of small strategically placed pallidal and medial thalamic lesions that serve to make subcritical the increased low frequency thalamocortical recurrent network activity. This result is attained via reduction of both thalamic overinhibition and low frequency over-synchronization. Thalamic disinhibition is obtained by a lesion in the anterior medial paralimbic pallidum. The medial thalamic lesion is localized in the posterior part of the central lateral nucleus, where a large majority of cells have been shown to be locked in low frequency production and to have lost their normal activation patterns. We present here our experience with 11 patients, including clinical follow ups and pre- and postsurgical magnetoencephalographic studies. The evidence speaks (1) for a benign and efficient surgical approach, and (2) for the relevance of the patient’s presurgical cognitive and social settings, making them more or less prone to postoperative psychoreactive manifestations upon rekindling of personal goals and social reentry.
A comparison of M1 and M4 muscarinic receptors in the thalamus from control subjects and subjects with schizophrenia
- B. Dean, L. Gray, D. Keriakous, E. Scarr
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- 18 April 2006, pp. 287-295
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Having shown a decrease in muscarinic M1 receptors in Brodmann’s area (BA) 9 from subjects with schizophrenia we have extended our studies to determine if this receptor is decreased in the thalamus from the same cohort of subjects. Levels of [3H]pirenzepine binding to and mRNA encoding for M1 and M4 receptors were measured throughout the thalamus. Levels of M1 and M4 receptor proteins were measured in the mediodorsal nucleus. Two-way ANOVA revealed a variance in [3H]pirenzepine binding (F = 4.69, d.f. = 1.190, P = 0.03), but there was no significant change in radioligand binding in any thalamic region in schizophrenia. Neither levels of mRNA encoding the thalamic M1 or M4 receptor nor levels of M1 or M4 receptor protein in the mediodorsal nucleus differed between the schizophrenic and control subjects. We therefore conclude that the M1 and M4 receptor are not altered in the thalamus from subjects with schizophrenia. These data add weight to the hypothesis that changes in M1 receptors in selective regions of the CNS are associated with the pathology of schizophrenia.
Pathways for emotions and memory I. Input and output zones linking the anterior thalamic nuclei with prefrontal cortices in the rhesus monkey
- D. Xiao, H. Barbas
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- 18 April 2006, pp. 21-32
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The anterior thalamic nuclei occupy a central position in pathways associated with emotions and memory [AMA Arch. Neurol. Psychiatry 38 (1937) 725]. The goal of this study was to determine the anatomic interaction of the anterior nuclei with distinct prefrontal cortices that have been implicated in emotion and specific aspects of memory. To address this issue, we investigated the relationship of input and output zones in the anterior thalamic nuclei linking them with functionally distinct orbitofrontal, medial, and lateral prefrontal cortices. We identified input zones by mapping the pattern and topography of terminations of prefrontal axons, and the output zones by mapping projection neurons in the anterior nuclei, after injection of anterograde and bidirectional tracers in distinct prefrontal cortices.
The results showed that the anterior nuclei were preferentially connected with some orbitofrontal and medial prefrontal areas. In contrast, the anterior nuclei had comparatively sparse connections with most lateral prefrontal cortices, with the notable exception of frontal polar cortex, which had moderate but consistent connections with the anterior nuclei. Prefrontal cortices were connected mostly with the anterior medial nucleus, though medial areas 32 and 25 as well as the frontal polar cortex were also connected with the anterior ventral nucleus. The zones of axonal terminations were more expansive than the sites with projection neurons in the anterior nuclei, suggesting extensive influence of feedback projections from prefrontal cortices. The results suggest that the anterior thalamic nuclei may act in concert with orbitofrontal and medial prefrontal cortices in processes underlying emotions and long-term memory, and with the frontal polar cortex in prospective aspects of working memory.
Thalamic theta field potentials and EEG: high thalamocortical coherence in patients with neurogenic pain, epilepsy and movement disorders
- J. Sarnthein, A. Morel, A. von Stein, D. Jeanmonod
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- 18 April 2006, pp. 231-238
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We simultaneously recorded local field potentials (LFP) in the thalamus and EEG on the scalp of 17 patients suffering from neurogenic pain, epilepsy and movement disorders. The EEG of 11 patients displayed enhanced power in the theta frequency range (4–8 Hz). The thalamic LFP of 14 patients peaked in the theta range. The theta coherence between EEG and LFP was significant for 12 patients and reached strengths up to 70%. These findings suggest that enhanced theta rhythmicity occurs in tight functional thalamocortical loops and is a major element in all three diseases investigated.
To investigate second-order phase-coupling between LFP frequency components, we computed the bicoherence and averaged over the group of patients. We found peaks in the theta band and the beta band (14–30 Hz), indicating phase correlations of oscillatory events in these frequency ranges with their first harmonic. A further peak indicates that phase coupling occurred also between theta and beta frequencies. This indicates a strong functional interaction between the generators of these oscillations. We also computed the cross-correlation between LFP spectral power at different frequencies. Although this measure is independent of phase, we found good agreement with the bicoherence patterns, pointing again to strong interaction between theta and beta rhythmicity. The overproduction of theta rhythms, the thalamocortical coherence and the correlation of theta with beta rhythms are key elements for the understanding of thalamocortical dysrhythmia (TCD).
Mini-review
The developmental decrease in REM sleep
- E. Garcia-Rill, T. Kobayashi, C. Good
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- 18 April 2006, pp. 115-131
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This mini-review considers certain factors related to the developmental decrease in rapid eye movement (REM) sleep, including its timing, its relationship to other developmental changes, factors that may influence its progress and its potential role in brain development. Specifically, we discuss some of the theories proposed for its occurrence and agree with the classic notion that REM sleep is, at least, an active mechanism that may play a role in the maturation of the central nervous system (CNS), specifically contributing to the maturation of thalamocortical pathways. The developmental decrease in REM sleep occurs gradually from birth until after puberty in the human, but in other mammals it is brief and coincides with eye and ear opening and the beginning of massive exogenous activation. This purported role for REM sleep may change to involve a number of other functions with age. We describe recent findings showing that intrinsic morphological and physiological properties as well as serotonergic, n-methyl-D-aspartic acid (NMDA) and kainic acid (KA) synaptic inputs to mesopontine cholinergic neurons change dramatically at this critical period in development, perhaps driving what has been proposed as a REM sleep inhibitory process (RIP). We hypothesize that a dysregulation of this process could result in life-long disturbances in REM sleep drive, leading to hypervigilance or hypovigilance such as that observed in a number of disorders which have a mostly postpubertal age of onset. Finally, we also hypothesize that the role of normal cyclic increases in vigilance, observable during both sleep and waking, may be related, at least in part, to cortical blood flow.
Research Article
Thalamus in flame: targeting of infectious agents to thalamic nuclei
- Marina Bentivoglio, Krister Kristensson
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- 18 April 2006, pp. 297-314
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The involvement of the thalamus in infectious diseases of the nervous system has been hitherto rather neglected by investigators in clinical and basic neuroscience, despite numerous reports indicating that the thalamus, and territories within this region, can be attacked by different types of microbes. This topic is here reviewed. First, an overview is provided on general principles of spread of microbes to the brain (through peripheral nerves, or through the blood or cerebrospinal fluid) and their interactions with neurons and immune cells to cause acute, transient or persistent infections. Examples are given on how non-cytolytic infections can cause long-lasting disturbances in synaptic activities and neuronal networks as a result of a “hit-and-run” mechanism, or as an effect of factors released in the microenvironment to control the neuronal infection. Emerging data on how molecules functioning at the “immunological synapse” (the site of contact between immune cells and target infected cells) may affect nervous system synapses are pointed out. An account is then given of clinical and experimental infections of the thalamus caused by viruses (rabies and herpes viruses, influenza A virus, flaviviruses, HIV virus), the parasite Toxoplasma gondii, and prions. The implications and consequences of the attack of these microbes to the thalamus are discussed. Of special interest is the potential persistence of latent infections in thalamic neurons, which could cause disturbances of neuronal functions in the absence of overt structural lesions. Altogether these data recall attention on the pathogenesis and consequences of acute and persistent infections in the mammalian thalamus.
Pathways for emotions and memory II. Afferent input to the anterior thalamic nuclei from prefrontal, temporal, hypothalamic areas and the basal ganglia in the rhesus monkey
- D. Xiao, H. Barbas
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- 18 April 2006, pp. 33-48
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The anterior thalamic nuclei are a key link in pathways associated with emotions and memory. In the preceding study we found that one of the anterior nuclei, the anterior medial (AM), had particularly robust connections with specific medial prefrontal and orbitofrontal cortices and moderate connections with frontal polar cortices. The goal of this study was to use a direct approach to determine the sources of projections to the AM nucleus from all prefrontal cortices, as well as from temporal structures and the hypothalamic mammillary body, known for their role in distinct aspects of memory and emotion. We addressed this issue with targeted injections of retrograde fluorescent tracers in the AM nucleus to determine its sources of input.
Projection neurons directed to the AM nucleus were found in the deep layers of most prefrontal cortices (layers V and VI), and were most densely distributed in medial areas 24, 32 and 25, orbitofrontal areas 13 and 25, and lateral areas 10 and 46. Most projection neurons were found in layer VI, though in medial prefrontal cortices and dorsal area 9 about a third were found in layer V, a significantly higher proportion than in lateral and orbitofrontal cortices. In the temporal lobe, projection neurons originated mostly from the hippocampal formation (ammonic field CA3 and subicular complex), and the amygdala (basolateral, lateral, and basomedial nuclei). In the hypothalamus, a significant number of neurons in the ipsilateral medial mammillary body projected to the AM nucleus, some of which were positive for calbindin (CB) or parvalbumin (PV), markers expressed, respectively, in “diffuse” and “specific” pathways in the thalamus [Adv. Neurol. 77 (1998a) 49]. As recipient of diverse signals, the AM nucleus is in a key position to link pathways associated with emotions, and may be an important interface for systems associated with retrieval of information from long-term memory in the process of solving problems within working memory. Finally, the internal segment of the globus pallidus (GPi) issued projections to AM, suggesting direct linkage with executive systems through the basal ganglia. The diverse connections of the AM nucleus may help explain the varied deficits in memory and emotions seen in neurodegenerative and psychiatric diseases affecting the anterior thalamic nuclei.
Anterior thalamic unit discharge profiles and coherence with hippocampal theta rhythm
- Zimbul Albo, Gonzalo Viana Di Prisco, Robert Vertes
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- 18 April 2006, pp. 133-144
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The anterior thalamus (ATh) is a key structure of the limbic system and serves a direct role in spatial memory. We examined the discharge properties of neurons of the anterior thalamus during states of the hippocampal electroencephalogram (theta and non-theta states). Units were recorded in the anteroventral (AV, n = 96), the anterodorsal (AD, n = 44) and the anteromedial (AM, n = 48) nuclei of the thalamus. The majority of theta-related cells fired at higher rates in the presence than absence of theta (theta-on cells); while a small percentage (∼ 13%) discharge at reduced rates with theta (theta-off cells). Theta-off cells were found in AD and AM but not in AV. Mean discharge rates for theta-on cells during control and theta conditions were 6.0 plusmn; 0.52 and 14.48 plusmn; 0.96 Hz for AV cells; 4.43 plusmn; 1.25 and 10.05 plusmn; 1.28 Hz for AD cells, and 2.60 plusmn; 0.3 and 6.42 plusmn; 0.9 Hz for AM cells. Approximately 40% of AV cells, 21.9% of AD units, and 5.7% of AM cells discharged rhythmically, synchronous with the theta rhythm. A subpopulation of ATh cells fired slightly rhythmicity, but with activity strongly phase-locked to EEG oscillations in the crosscorrelogram, indicating a modulation at theta frequency. Cells were classified as: rhythmic (R), non-rhythmic (N, and intermediate (I) based on quantitative criteria. About 75% of theta-on cells (i.e. R and I cells) showed significant coherence with theta. These cells were distributed throughout the extent of the anterior thalamus. The present findings of theta rhythmic cells in the anterior thalamus, together with previous demonstrations of ‘theta’ cells in other structures of Papez’s circuit, suggests that a theta rhythmic signal may reverberate throughout the circuit, possibly involved in memory processing functions of this limbic network.
Developmental decrease in REM sleep: the shift to kainate receptor regulation
- T. Kobayashi, R.D. Skinner, E. Garcia-Rill
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- 18 April 2006, pp. 315-324
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We found a shift in the responsiveness of pedunculopontine neurons from N-methyl-D-aspartic acid (NMDA) to kainic acid (KA) regulation around 15 days of age. While rapid eye movement (REM) sleep in humans decreases from 50 to 15% of sleep time between birth and the end of puberty, a similar decrease in the rat occurs from 10 to 30 days postnatally. Intracellularly recorded type II cholinergic PPN neurons, known to modulate waking and REM sleep, showed a gradual decrease in responsiveness to NMDA, and an increase in responsiveness to KA, during this period. Non-cholinergic PPN neurons did not show a developmental-dependent change in responsiveness. These results do not help explain if KA and NMDA control the developmental decrease in REM sleep, however, the data indicate that the shift at ∼15 days suggests that REM sleep becomes selectively modulated by KA receptors in the adult. Therefore, given development of appropriate compounds, KA receptor antagonism may become an effective treatment for disorders that manifest increased REM sleep drive and produce frequent nocturnal arousals and awakenings, e.g. schizophrenia, anxiety, insomnia, etc.
Thalamic neuropathology in the chronic pilocarpine and picrotoxin model of epilepsy
- Clement Hamani, Luiz Mello
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- 18 April 2006, pp. 49-53
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Adult male Wistar rats were injected with 150/0.5, 75/1.5 and 50/2.0 mg/kg of pilocarpine (Pilo) and picrotoxin (PTX) (Pilo/PTX mg/kg). The vast majority of the animals developed status epilepticus (SE), after which they were observed for a period of 120–131 days for the occurrence of spontaneous recurrent seizures (SRS). After the experiments, animals were deeply anesthetized, perfused with a 10% formaldehyde fixative solution and their brains were processed with cresyl violet, Perls and Von Kossa techniques. Cell counts were performed under a regular microscopic grid in diverse anteroposterior levels of the thalamus. Several thalamic nuclei in the epileptic groups, particularly the central medial, central lateral, paracentral, mediodorsal, laterodorsal and lateroposterior, showed intense cell loss, pathologic calcification and iron tissue deposits. Our results are relevant to support the importance of the thalamus in the pathogenesis of the epilepsies.
Comparative physiological and serotoninergic properties of pulvinar neurons in the monkey, cat and ferret
- James E. Monckton, David A. McCormick
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- 18 April 2006, pp. 239-252
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The basic electrophysiological properties and responses to serotonin of thalamocortical (TC) neurons in the ferret, cat, and monkey pulvinar were compared. Morphologically, thalamocortical neurons in these three species were similar, except for the presence of beaded dendrites in many monkey neurons. In all three species, the neurons exhibited two distinct firing modes: single spike activity and low threshold Ca2+-spike mediated bursting. However, in monkeys, the low threshold Ca2+ spikes were followed by a prominent 50–100 ms afterhyperpolarization that could result in the generation of an additional rebound Ca2+ spike. The application of 5-HT to thalamocortical neurons in cat and monkey pulvinar resulted in a depolarization and an increase in membrane conductance through an enhancement of the hyperpolarization-activated cation current, Ih, apparently through the activation of 5-HT7 receptors. In contrast, the application of serotonin to ferret pulvinar neurons resulted in a prominent hyperpolarization, owing to an increase in membrane potassium conductance. In monkey and ferret, application of serotonin could result in barrages of IPSPs in thalamocortical neurons. These results indicate that there are significant species-dependent differences in both the electrophysiological and pharmacological properties of pulvinar thalamocortical neurons.