Substantia Innominata Research Articles

Elucidation of White Matter Tracts of the Human Amygdala by Detailed Comparison between High-Resolution Postmortem Magnetic Resonance Imaging and Histology.

The amygdala has attracted considerable research interest because of its potential involvement in various neuropsychiatric disorders. Recently, attempts have been made using magnetic resonance imaging (MRI) to evaluate the integrity of the axonal connections to and from the amygdala under pathological conditions. Although amygdalar pathways have been studied extensively in animal models, anatomical references for the human brain are limited to histology-based resources from a small number of slice locations, orientations and annotations. In the present study, we performed high-resolution (250 μm) MRI of postmortem human brains followed by serial histology sectioning. The histology data were used to identify amygdalar pathways, and the anatomical delineation of the assigned structures was extended into 3D using the MRI data. We were able to define the detailed anatomy of the stria terminalis and amygdalofugal pathway, as well as the anatomy of the nearby basal forebrain areas, including the substantia innominata. The present results will help us understand in detail the white matter structures associated with the amygdala, and will serve as an anatomical reference for the design of in vivo MRI studies and interpretation of their data.

Descending projections from the basal forebrain to the orexin neurons in mice.

The orexin (hypocretin) neurons play an essential role in promoting arousal, and loss of the orexin neurons results in narcolepsy, a condition characterized by chronic sleepiness and cataplexy. The orexin neurons excite wake-promoting neurons in the basal forebrain (BF), and a reciprocal projection from the BF back to the orexin neurons may help promote arousal and motivation. The BF contains at least three different cell types (cholinergic, glutamatergic, and γ-aminobutyric acid (GABA)ergic neurons) across its different regions (medial septum, diagonal band, magnocellular preoptic area, and substantia innominata). Given the neurochemical and anatomical heterogeneity of the BF, we mapped the pattern of BF projections to the orexin neurons across multiple BF regions and neuronal types. We performed conditional anterograde tracing using mice that express Cre recombinase only in neurons producing acetylcholine, glutamate, or GABA. We found that the orexin neurons are heavily apposed by axon terminals of glutamatergic and GABAergic neurons of the substantia innominata (SI) and magnocellular preoptic area, but there was no innervation by the cholinergic neurons. Channelrhodopsin-assisted circuit mapping (CRACM) demonstrated that glutamatergic SI neurons frequently form functional synapses with the orexin neurons, but, surprisingly, functional synapses from SI GABAergic neurons were rare. Considering their strong reciprocal connections, BF and orexin neurons likely work in concert to promote arousal, motivation, and other behaviors. J. Comp. Neurol. 525:1668-1684, 2017. © 2016 Wiley Periodicals, Inc.

Cognitive and Neuroanatomical Correlates in Early Versus Late Onset Parkinson's Disease Dementia.

Aging is the most important risk factor of development of dementia in Parkinson's disease (PD), but there are no data on clinical and radiological heterogeneity of PD dementia (PDD) depending on age at onset. The goal of this study was to examine whether patients with PDD are clinically and radiologically heterogeneous depending on age at onset. A total of 116 patients with PD dementia and 121 age- and sex-matched normal controls were enrolled. The subjects were divided into early-onset (EOPDD; n = 39) and late-onset (LOPDD; n = 77) PDD with the respective age-matched control group based on a cutoff value of 70 years. The effects of diagnosis, age, and their interaction on neuropsychological tests, cortical thickness, and substantia innominata volume were assessed using analysis of covariance. EOPDD patients had a poorer cognitive performance on digit backward, forward span test (p = 0.011 and 0.05), and visual recognition memory function (p = 0.012) compared with LOPDD patients. Additionally, EOPDD patients exhibited cortical thinning in the left anterior cingulate gyrus and the right inferior temporal gyrus, with significantly decreased normalized substantia innominata volume (p = 0.044). Our data demonstrated that EOPDD patients exhibit poorer cognitive performance and more severe atrophy in the cortex and substantia innominata, implying that EOPDD may be a distinct phenotype different from LOPDD.

The cholinergic forebrain arousal system acts directly on the circadian pacemaker

Sleep and wake states are regulated by a variety of mechanisms. One such important system is the circadian clock, which provides temporal structure to sleep and wake. Conversely, changes in behavioral state, such as sleep deprivation (SD) or arousal, can phase shift the circadian clock. Here we demonstrate that the level of wakefulness is critical for this arousal resetting of the circadian clock. Specifically, drowsy animals with significant power in the 7- to 9-Hz band of their EEGs do not exhibit phase shifts in response to a mild SD procedure. We then show that treatments that both produce arousal and reset the phase of circadian clock activate (i.e., induce Fos expression in) the basal forebrain. Many of the activated cells are cholinergic. Using retrograde tract tracing, we demonstrate that cholinergic cells activated by these arousal procedures project to the circadian clock in the suprachiasmatic nuclei (SCN). We then demonstrate that arousal-induced phase shifts are blocked when animals are pretreated with atropine injections to the SCN, demonstrating that cholinergic activity at the SCN is necessary for arousal-induced phase shifting. Finally, we demonstrate that electrical stimulation of the substantia innominata of the basal forebrain phase shifts the circadian clock in a manner similar to that of our arousal procedures and that these shifts are also blocked by infusions of atropine to the SCN. These results establish a functional link between the major forebrain arousal center and the circadian system.

Microsurgical and Fiber Tract Anatomy of the Nucleus Accumbens.

The nucleus accumbens (NAc) has been a target for deep brain stimulation (DBS) in the treatment of depression and obsessive-compulsive disorder (OCD). To examine the anatomy and connections of the NAc using a fiber dissection technique. Ten human brains and 2 whole cadaveric heads were examined by fiber dissection technique and ×6 to ×40 surgical magnification. The NAc was examined from the lateral, medial, superior, and inferior sides to define its fiber connections and relationships with adjacent cortical and subcortical structures. Magnetic resonance imaging (MRI) with 1-mm slices was used to define its neuronavigation coordinates. Eight tracts, the uncinate fasciculus, cingulum, stria medullaris thalami, fornix, diagonal band of Broca, stria terminalis, medial olfactory stria, and forceps minor, form a capsule around the anterior, inferior, and medial sides of the NAc. The uncinate fasciculus connects along the inferior and adjacent part of the medial side of the NAc, the cingulum and diagonal band along the medial surface, the medial olfactory stria along the posteromedial and adjacent part of the inferior surface, the forceps minor along the anteromedial surface, and the stria terminalis, fornix, and stria medullaris along the posterosuperior surface. The subcortical gray matter related to the NAc includes the septal nuclei, indusium griseum, substantia innominata, caudate nucleus, and hypothalamus. The cortical areas communicating with and overlying the NAc are reviewed. An increased understanding of the fiber connections and neural relationships of the NAc should allow more accurate DBS targeting for the treatment of psychiatric disorders.

The Foxb1‐expressing neurons of the ventrolateral hypothalamic parvafox nucleus project to defensive circuits

ABSTRACTThe parvafox nucleus is an elongated structure that is lodged within the ventrolateral hypothalamus and lies along the optic tract. It comprises axially located parvalbumin (Parv)‐positive neurons and a peripheral cuff of Foxb1‐expressing ones. In the present study, injections of Cre‐dependent adenoviral constructs were targeted to the ventrolateral hypothalamus of Foxb1/Cre mice to label specifically and map the efferent connections of the Foxb1‐expressing subpopulation of neurons of the parvafox nucleus. These neurons project more widely than do the Parv‐positive ones and implicate a part of the axons known to emanate from the lateral hypothalamus. High labeling densities were found in the dorsolateral and the upper lateral portion of the periaqueductal gray (PAG), the Su3 and PV2 nuclei of the ventrolateral PAG, the cuneiform nucleus, the mesencephalic reticular formation, and the superior colliculus. Intermediate densities of terminals were encountered in the septum, bed nucleus of the stria terminalis, substantia innominata, various thalamic and hypothalamic nuclei, pedunculopontine nucleus, Barrington's nucleus, retrofacial nucleus, and retroambigual nucleus. Scattered terminals were observed in the olfactory bulbs, the prefrontal cortex and the lamina X of the cervical spinal cord. Because the terminals were demonstrated to express the glutamate transporter VGlut2, the projections are presumed to be excitatory. A common denominator of the main target sites of the Foxb1‐positive axons of the parvafox nucleus appears to be an involvement in the defensive reactions to life‐threatening situations. The hypothalamic parvafox nucleus may contribute to the autonomic manifestations that accompany the expression of emotions. J. Comp. Neurol. 524:2955–2981, 2016. © 2016 Wiley Periodicals, Inc.

Consolidation of altered associability information by amygdala central nucleus

The surprising omission of a reinforcer can enhance the associability of the stimuli that were present when the reward prediction error was induced, so that they more readily enter into new associations in the future. Previous research from this laboratory identified brain circuit elements critical to the enhancement of stimulus associability by the omission of an expected event and to the subsequent expression of that altered associability in more rapid learning. These elements include the amygdala, the midbrain substantia nigra, the basal forebrain substantia innominata, the dorsolateral striatum, the secondary visual cortex, and the posterior parietal cortex. Here, we found that consolidation of a surprise-enhanced associability memory in a serial prediction task depends on processing in the amygdala central nucleus (CeA) after completion of sessions that included the surprising omission of an expected event. Post-surprise infusions of anisomycin, lidocaine, or muscimol prevented subsequent display of surprise-enhanced associability. Because previous studies indicated that CeA function is unnecessary for the expression of associability enhancements that were induced previously when CeA function was intact (Holland & Gallagher, 2006), we interpreted these results as indicating that post-surprise activity of CeA (“surprise replay”) is necessary for the consolidation of altered associability memories elsewhere in the brain, such as the posterior parietal cortex (Schiffino et al., 2014a).

The Foxb1-expressing neurons of the ventrolateral hypothalamic parvafox nucleus project to defensive circuits.

The parvafox nucleus is an elongated structure that is lodged within the ventrolateral hypothalamus and lies along the optic tract. It comprises axially located parvalbumin (Parv)-positive neurons and a peripheral cuff of Foxb1-expressing ones. In the present study, injections of Cre-dependent adenoviral constructs were targeted to the ventrolateral hypothalamus of Foxb1/Cre mice to label specifically and map the efferent connections of the Foxb1-expressing subpopulation of neurons of the parvafox nucleus. These neurons project more widely than do the Parv-positive ones and implicate a part of the axons known to emanate from the lateral hypothalamus. High labeling densities were found in the dorsolateral and the upper lateral portion of the periaqueductal gray (PAG), the Su3 and PV2 nuclei of the ventrolateral PAG, the cuneiform nucleus, the mesencephalic reticular formation, and the superior colliculus. Intermediate densities of terminals were encountered in the septum, bed nucleus of the stria terminalis, substantia innominata, various thalamic and hypothalamic nuclei, pedunculopontine nucleus, Barrington's nucleus, retrofacial nucleus, and retroambigual nucleus. Scattered terminals were observed in the olfactory bulbs, the prefrontal cortex and the lamina X of the cervical spinal cord. Because the terminals were demonstrated to express the glutamate transporter VGlut2, the projections are presumed to be excitatory. A common denominator of the main target sites of the Foxb1-positive axons of the parvafox nucleus appears to be an involvement in the defensive reactions to life-threatening situations. The hypothalamic parvafox nucleus may contribute to the autonomic manifestations that accompany the expression of emotions. J. Comp. Neurol. 524:2955-2981, 2016. © 2016 Wiley Periodicals, Inc.

NEUROPATHOLOGY OF FAMILIAL ALZHEIMER'S DISEASE ASSOCIATED WITH A PRESENILIN 1 A396T MUTATION REVEALS THE COEXISTENCE OF Aβ, TAU, AND A-SYNUCLEIN PROTEINOPATHIES

In the course of a published, large molecular study of Alzheimer disease in Turkey, the Presenilin 1 (PSEN1) variant GCC to ACC was identified at c.1186 in the coding region of Exon 11. The same DNA change was found by analyzing archival brain tissue obtained by the National Cell Repository for Alzheimer’s Disease. A re-examination of the brain was carried out and available clinical records reviewed. DNA was isolated from frozen brain tissue and the APP and PSEN1 genes were sequenced. For histology, the following methods were used: Hematoxylin Eosin, Woelcke-Heidenhain, and Bielschowsky; for immunohistochemistry, antibodies against tau (ALZ-50), amyloid β (10D5), and α-synuclein were used. A 58 year old male complained of problems of concentration. At age 60, he noted word finding problems. An MRI, at age 61, showed atrophy and white matter changes more pronounced in the right occipital lobe; a SPECT scan at age 62 showed decreased perfusion in the right parietal lobe. The subject died at age 66. The subject’s father developed a dementing illness after age 65. The fresh brain weighed 1200 grams. The left hemibrain was examined neuropathologically, while the right hemibrain was frozen for molecular studies. Histologic and immuno-histochemical studies revealed numerous Lewy bodies and neurites in cingulate, frontal, insular, temporal, parietal and occipital cortices, in hippocampus, caudate nucleus, putamen, substantia innominata, amygdala, thalamus, substantia nigra, ocular motor nerve nucleus, locus coeruleus, and nucleus ambiguus. Numerous neurofibrillary tangles and neuritic plaques, tau immuno-positive neurons and neuropril threads, as well as Aβ immuno-positive plaques were also present in the above mentioned anatomical regions. Aβ angiopathy was noted. DNA analysis revealed a GCC>ACC point mutation predicting an amino acid substitution of Alanine (A) to Threonine (T) at residue 396 in Presenilin 1. This is the first study of the neuropathologic features associated with the PSEN1 A396T mutation. The neuropathologic diagnoses established prior to molecular analysis were: 1) Lewy body disease and 2) Alzheimer disease. The reexamination forces us to reconsider the neuropathologic diagnosis and potential pathogenetic mechanisms operating in the presence of PSEN1 mutations. Acknowledgements: P30 AG 010133; U24 AG 21886.

Structural grey matter changes in the substantia innominata in Alzheimer's disease and dementia with Lewy bodies: a DARTEL-VBM study.

ObjectivesSeveral cholinergic nuclei, and in particular the nucleus basalis of Meynert, are localised to the substantia innominata in the basal forebrain. These nuclei provide major cholinergic innervation to the cerebral cortex and hippocampus, and have an essential role in cognitive function. The aim of this study was to investigate volumetric grey matter (GM) changes in the substantia innominata from structural T1 images in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and healthy older participants using voxel‐based morphometry.MethodsParticipants (41 DLB, 47 AD and 39 controls) underwent 3 T T1 magnetic resonance imaging and cognitive assessments. Voxel‐based morphometry analysis used SPM8 with a substantia innominata brain mask to define the subspace for voxel GM analyses. Group differences, and selected behavioural and clinical correlates, were assessed.ResultsCompared with that in controls, bilateral GM loss in the substantia innominata was apparent in both AD and DLB. Relative to controls, significant bilateral GM loss in the substantia innominata was observed in DLB and AD. In DLB, significant associations were also observed between substantia innominata GM volume loss, and the levels of cognitive impairment and severity of cognitive fluctuations.ConclusionsRelative to that controls, atrophy of the substantia innominata was apparent in DLB and AD, and is associated with specific clinical manifestations in DLB. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

Basal Forebrain Cholinergic-Auditory Cortical Network: Primary Versus Nonprimary Auditory Cortical Areas.

Acetylcholine (ACh) release in the cortex is critical for learning, memory, attention, and plasticity. Here, we explore the cholinergic and noncholinergic projections from the basal forebrain (BF) to the auditory cortex using classical retrograde and monosynaptic viral tracers deposited in electrophysiologically identified regions of the auditory cortex. Cholinergic input to both primary (A1) and nonprimary auditory cortical (belt) areas originates in a restricted area in the caudal BF within the globus pallidus (GP) and in the dorsal part of the substantia innominata (SId). On the other hand, we found significant differences in the proportions of cholinergic and noncholinergic projection neurons to primary and nonprimary auditory areas. Inputs to A1 projecting cholinergic neurons were restricted to the GP, caudate-putamen, and the medial part of the medial geniculate body, including the posterior intralaminar thalamic group. In addition to these areas, afferents to belt-projecting cholinergic neurons originated from broader areas, including the ventral secondary auditory cortex, insular cortex, secondary somatosensory cortex, and the central amygdaloid nucleus. These findings support a specific BF projection pattern to auditory cortical areas. Additionally, these findings point to potential functional differences in how ACh release may be regulated in the A1 and auditory belt areas.

Topographic organization of the basal forebrain projections to the perirhinal, postrhinal, and entorhinal cortex in rats.

Previous studies have shown that the basal forebrain (BF) modulates cortical activation via its projections to the entire cortical mantle. However, the organization of these projections is only partially understood or, for certain areas, unknown. In this study, we examined the topographic organization of cholinergic and noncholinergic projections from the BF to the perirhinal, postrhinal, and entorhinal cortex by using retrograde tracing combined with choline acetyltransferase (ChAT) immunohistochemistry in rats. The perirhinal and postrhinal cortex receives major cholinergic and noncholinergic input from the caudal BF, including the caudal globus pallidus and substantia innominata and moderate input from the horizontal limb of the diagonal band, whereas the entorhinal cortex receives major input from the rostral BF, including the medial septum and the vertical and horizontal limbs of the diagonal band. In the perirhinal cases, cholinergic projection neurons are distributed more caudally in the caudal globus pallidus than noncholinergic projection neurons. Compared with the perirhinal cases, the distribution of cholinergic and noncholinergic neurons projecting to the postrhinal cortex shifts slightly caudally in the caudal globus pallidus. The distribution of cholinergic and noncholinergic neurons projecting to the lateral entorhinal cortex extends more caudally in the BF than to the medial entorhinal cortex. The ratio of ChAT-positive projection neurons to total projection neurons is higher in the perirhinal/postrhinal cases (26-48%) than in the entorhinal cases (13-30%). These results indicate that the organization of cholinergic and noncholinergic projections from the BF to the parahippocampal cortex is more complex than previously described. J. Comp. Neurol. 524:2503-2515, 2016. © 2016 Wiley Periodicals, Inc.

Dynorphin inhibits basal forebrain cholinergic neurons by pre- and postsynaptic mechanisms.

The basal forebrain is an important component of the ascending arousal system and may be a key site through which the orexin neurons promote arousal. It has long been known that orexin-A and -B excite basal forebrain cholinergic neurons, but orexin-producing neurons also make the inhibitory peptide dynorphin. Using whole-cell recordings in brain slices, we found that dynorphin-A directly inhibits basal forebrain cholinergic neurons via κ-opioid receptors, and decreases afferent excitatory synaptic input to these neurons. While the effects of dynorphin-A and orexin-A desensitize over multiple applications, co-application of dynorphin-A and orexin-A produces a sustained response that reverses depending on the membrane potential of basal forebrain cholinergic neurons. At -40mV the net effect of the co-application is inhibition by dynorphin-A, whereas at -70mV the excitatory response to orexin-A prevails. The basal forebrain (BF) is an essential component of the ascending arousal systems and may be a key site through which the orexin (also known as hypocretin) neurons drive arousal and promote the maintenance of normal wakefulness. All orexin neurons also make dynorphin, and nearly all brain regions innervated by the orexin neurons express kappa opiate receptors, the main receptor for dynorphin. This is remarkable because orexin excites target neurons including BF neurons, but dynorphin has inhibitory effects. We identified the sources of dynorphin input to the magnocellular preoptic nucleus and substantia innominata (MCPO/SI) in mice and determined the effects of dynorphin-A on MCPO/SI cholinergic neurons using patch-clamp recordings in brain slices. We found that the orexin neurons are the main source of dynorphin input to the MCPO/SI region, and dynorphin-A inhibits MCPO/SI cholinergic neurons through κ-opioid receptors by (1) activation of a G protein-coupled inwardly rectifying potassium current, (2) inhibition of a voltage-gated Ca(2+) current and (3) presynaptic depression of the glutamatergic input to these neurons. The responses both to dynorphin-A and to orexin-A desensitize, but co-application of dynorphin-A and orexin-A produces a sustained response. In addition, the polarity of the response to the co-application depends on the membrane potential of BF neurons; at -40mV the net effect of the co-application is inhibition by dynorphin-A, whereas at -70mV the excitatory response to orexin-A prevails. This suggests that depending on their state of activation, BF cholinergic neurons can be excited or inhibited by signals from the orexin neurons.

A 100-year history of dementia with Lewy bodies

It takes more than one hundred years to understand dementia with bodies (DLB). Frederick Henry Lewy, a Germany doctor who studied the neuropathology of Parkinson's disease (PD) at Munich University, described eosinophilic intracytoplasmic inclusions in the dorsal vagal nuclei and substantia innominata of PD brains in 1912 for the first time. These inclusions were later named as Lewy body (LB) by a Russian neuropathologist Konstantin Tretiakoff in 1919. A Japanese researcher, Okazaki, correlated dementia to cortical LB in 1961. Kosaka proposed the term Lewy body disease (LBD) for the first time in 1980. Subsequently, more and more researchers delivered case reports and detailed classification of LBD. In 1995, the first Consortium on DLB International Workshop made the unitary denomination of this disease entity and established consensus guidelines for the clinical and pathological diagnosis of DLB. The diagnostic criteria were revised in 2003. Though the history of DLB study is similar to Alzheimer's disease (AD), DLB is still less recognized and needs further research. DOI: 10.3969/j.issn.1672-6731.2015.07.003

Chronic sleep restriction induces long-lasting changes in adenosine and noradrenaline receptor density in the rat brain.

Although chronic sleep restriction frequently produces long-lasting behavioural and physiological impairments in humans, the underlying neural mechanisms are unknown. Here we used a rat model of chronic sleep restriction to investigate the role of brain adenosine and noradrenaline systems, known to regulate sleep and wakefulness, respectively. The density of adenosine A1 and A2a receptors and β-adrenergic receptors before, during and following 5days of sleep restriction was assessed with autoradiography. Rats (n=48) were sleep-deprived for 18hday(-1) for 5 consecutive days (SR1-SR5), followed by 3 unrestricted recovery sleep days (R1-R3). Brains were collected at the beginning of the light period, which was immediately after the end of sleep deprivation on sleep restriction days. Chronic sleep restriction increased adenosine A1 receptor density significantly in nine of the 13 brain areas analysed with elevations also observed on R3 (+18 to +32%). In contrast, chronic sleep restriction reduced adenosine A2a receptor density significantly in one of the three brain areas analysed (olfactory tubercle which declined 26-31% from SR1 to R1). A decrease in β-adrenergic receptors density was seen in substantia innominata and ventral pallidum which remained reduced on R3, but no changes were found in the anterior cingulate cortex. These data suggest that chronic sleep restriction can induce long-term changes in the brain adenosine and noradrenaline receptors, which may underlie the long-lasting neurocognitive impairments observed in chronic sleep restriction.

Structural and functional neuroimaging in patients with Parkinson's disease and visual hallucinations: A critical review.

Patients with Parkinson's disease (PD) may develop various non-motor symptoms (NMS) during the course of the illness and psychosis is one of the common NMS of PD. Visual hallucinations (VH) are the most common manifestation of psychosis in PD. The exact pathogenesis of VH in patients with PD is not clearly understood. Presence of VH has been described to be associated with rapid cognitive decline and increased nursing home placements in PD patients. A large number of structural and functional neuroimaging studies have been conducted to understand the cerebral basis of VH in PD. Structural imaging studies (Voxel Based Morphometry) have reported grey matter atrophy in multiple regions of the brain such as primary visual cortex, visual association cortex, limbic regions, cholinergic structures such as pedunculopontine nucleus and substantia innominata, which conclude possible alterations of brain regions associated with functions such as visuospatial-perception, attention control and memory. Most functional neuroimaging studies (functional MRI, positron emission tomography and single photon emission computerized tomography) have reported altered activation, blood flow, or reduced metabolism in both dorsal and ventral visual pathways, which probably indicates an alteration in the normal bottom-top visual processing and the presence of an aberrant top-down visual processing. This review critically analyzes the published studies on the structural and functional neuroimaging in PD patients with VH.

Amygdalo-striatal interaction in the enhancement of stimulus salience in associative learning.

Function of the central nucleus of the amygdala (CeA) is critical to 2 aspects of attention in associative learning: the conditioning of orienting responses (ORs) to cues paired with food, and the enhancement of cue salience by the surprising omission of expected events. Such salience enhancements have been found to depend on interactions within a circuit that includes CeA, the substantia nigra pars compacta (SNc), the substantia innominata (SI), and the posterior parietal cortex (PPC). The acquisition and expression of conditioned ORs requires interactions among CeA, SNc, and the dorsal lateral striatum (DLS), but not SI or PPC. Here, we considered whether CeA-DLS interactions are also important in surprise-induced salience enhancements in a serial prediction task. Rats received unilateral lesions of CeA and DLS, either contralaterally, which disrupted interactions between those structures, or ipsilaterally, which produced comparable damage to each structure but permitted interactions between them in 1 hemisphere. Rats with ipsilateral lesions of CeA and DLS showed the salience enhancements normally observed in this task, but rats with contralateral lesions of those structures did not. Thus, convergence of information processing by CeA and DLS is essential for surprise-induced salience enhancements, as well as for conditioned ORs.

Modulation of Synaptic Processes in Cortical Neurons in Response to Painful Stimulation and Analgesia

We studied effects of electrical stimulation of the substantia nigra (SN), locus coeruleus (LC), raphe nuclei (RN), substantia innominata (SIn), nucleus caudatus (NC) and central grey (CG) on postsynaptic processes evoked in neurons of the cat somatosensory cortex by excitation of nociceptive and non-nociceptive afferent inputs (intense stimulation of the dental pulp and moderate stimulation of the thalamic ventroposteromedial nucleus, VPMN, respectively). We analyzed intracellularly recorded activity of cortical cells activated exclusively by stimulation of nociceptors and cells activated by both nociceptive and non-nociceptive influences (“nociceptive” and convergent neurons). In neurons of both groups, stimulation of both nociceptive afferents and thalamic VPMN resulted in the development of successions of EPSP – action potential (AP) or their series – IPSP (IPSP duration 200–300 msec). Conditioning electrical stimulation the above-mentioned nuclei induced suppression of synaptic reactions that occur in cortical neurons in response to stimulation of nociceptive inputs. The maximum of inhibition was observed at test intervals of 600 to 800 msec. We observed certain parallelism between conditioning influentions of PAG activation and effects of systemic injections of morphine. Decrease in the amplitude or complete postsynaptic inhibition of IPSP in cortical neurons under different treatments associate with the occurrence of convulsive epileptic activity, and at the painful action with analgesic effect. Discussed are the mechanisms for modulatory influences exerted by conditioning stimulation of SN, LC, RN, NC, SIn and CG on the somatosensory neurons, activated upon excitation of high-threshold (nociceptive) afferent inputs.

Anatomical organization of MCH connections with the pallidum and dorsal striatum in the rat.

Neurons producing the melanin-concentrating hormone (MCH) are distributed in the posterior hypothalamus, but project massively throughout the forebrain. Many aspects regarding the anatomical organization of these projections are still obscure. The present study has two goals: first to characterize the topographical organization of neurons projecting into the cholinergic basal forebrain (globus pallidus, medial septal complex), and second to verify if MCH neurons may indirectly influence the dorsal striatum (caudoputamen) by innervating afferent sources to this structure. In the first series of experiments, the retrograde tracer fluorogold was injected into multiple sites in the pallidal and medial septal regions and the distribution of retrogradely labeled neurons were analyzed in the posterior lateral hypothalamus. In the second series of experiments, fluorogold was injected into the caudoputamen, and the innervation by MCH axons of retrogradely labeled cells was analyzed. Our results revealed that the MCH system is able to interact with the basal nuclei in several different ways. First, MCH neurons provide topographic inputs to the globus pallidus, medial septal complex, and substantia innominata. Second, striatal projecting neurons in the cortex, thalamus, and substantia nigra presumably receive only sparse inputs from MCH neurons. Third, the subthalamic nucleus is heavily innervated by MCH projections, thus, presumably serves as one important intermediate station to mediate MCH influence on other parts of the basal nuclei.

NEUROSTRUCTURAL CORRELATES OF COGNITION IN DEMENTIA WITH LEWY BODIES: A VBM-DARTEL STUDY

Background: The substantia innominata (SI) forms part of the basal forebrain that provides major cholinergic innervation to the cerebral cortex and hippocampus, and has an essential role in cognitive function. Cholinergic loss is a central feature of dementia with Lewy bodies (DLB) and contributes to the clinical symptom phenotype. The objective was to investigate grey matter (GM) and white matter (WM) changes in the SI from magnetic resonance (MR) images in DLB, Alzheimer’s disease (AD) and healthy older subjects using voxel-based morphometry (VBM).Methods:One hundred and twenty seven subjects’ (39 controls, 48 AD, 41 DLB) underwent 3T T1 MR imaging as well as clinical and cognitive assessments. VBM was undertaken using SPM8 and used a SI mask image to define the brain volume subspace for voxel analyses. Group differences in GM andWMvolumes and selected behavioural correlates were assessed using the general linear model, with age and total intracranial volume as nuisance variables. Effects were identified using an uncorrected threshold of P uncorrected 0.05, followed by family-wise error (FWE) correction for multiple comparisons (P FWE 0.05) within the SI volume subspace. Results: Relative to controls, VBM analysis revealed significant bilateral GM loss in the SI in both AD and DLB (P FWE 0.05); however, these deficits were more pronounced in DLB. Compared to controls, significant WM loss (P FWE 0.05) was also observed bilaterally in AD but not in DLB. In DLB, significant correlations were found withMMSE and CAF scores on GMvolume (P FWE 0.05). Conclusions: In DLB, GM loss is more pronounced in the SI than in AD and appears to be associated with dementia severity and cognitive fluctuations. GM atrophy of the SI may shed light in understanding some of the clinical manifestations of DLB, while relative preservation of WM volume could also have positive implications for cholinergic intervention.