A novel antimuscarinic agent, pirenzepine, has been proposed to distinguish at least two subtypes... more A novel antimuscarinic agent, pirenzepine, has been proposed to distinguish at least two subtypes of muscarinic receptor. M1 receptors have been designated as those displaying a high affinity for pirenzepine. Both functional and binding studies have revealed a prevalence of M1 receptors in sympathetic ganglia while autonomic effector tissues have only low densities of M1 receptors. In the present study, in vitro autoradiographic procedures have been used to localize specifically high affinity binding sites for pirenzepine (M1 receptors) in sections of guinea-pig ileum, rat superior cervical ganglion and rat submaxillary gland. The overall localization of muscarinic receptors was also studied using the non-selective antagonist, [3H]N-methylscopolamine. The highest densities of M1 receptors were found in superior cervical ganglion, sympathetic nerve bundles, myenteric ganglia and mucous secreting cells of the submaxillary gland, while lower densities were found in smooth muscle and serous secreting cells of the submaxillary gland. No area found to possess muscarinic receptors was devoid of M1 receptors.
The [3H]indalpine binding sites have been characterized in slide-mounted cat brain sections. This... more The [3H]indalpine binding sites have been characterized in slide-mounted cat brain sections. This inhibitor of 5-HT reuptake binds with a very high affinity to sites which have the pharmacological properties of the serotonin carrier. These sites can, however, be differentiated from the [3H]imipramine binding sites by their Na+ dependency and competitive inhibition by serotonin. Quantitative autoradiographic studies demonstrate that indalpine binding sites are localized in structures rich in serotonergic neurons. The widespread distribution of indalpine binding sites in limbic and associative areas is consisted with its well characterized antidepressant activity in human.
: The binding of [3H]indalpine {4‐[2‐(3‐indolyl)]ethyl piperidine} to slide‐mounted sections of r... more : The binding of [3H]indalpine {4‐[2‐(3‐indolyl)]ethyl piperidine} to slide‐mounted sections of rat brain has been characterized. This 5‐hydroxytryptamine (5‐HT) uptake blocker binds to sections with high affinity (KD∼ 1 nM). The binding is saturable, and can be displaced by the addition of clomipramine (1 μM). Other drugs inhibiting the uptake of 5‐HT also have the capacity to inhibit the binding of [3H]indalpine. A significant correlation (r = 0.86) was found between the capacity of these compounds to inhibit the uptake of 5‐HT and their potencies as inhibitors of [3H]indalpine binding. Binding was Na+‐ and Cl−dependent and was inhibited competitively by 5‐HT. Furthermore, electrolytic lesions of the dorsal raphe or medial forebrain bundle, which cause a degeneration of 5‐HT cell bodies and fibers, respectively, resulted in a 30–40% reduction in the binding of [3H]indalpine. [3H]Indalpine binds to the 5‐HT uptake recognition sites in a different manner from imipraminelike compounds.
: The localization of binding sites for [3H]indalpine to sections of rat brain was studied by a q... more : The localization of binding sites for [3H]indalpine to sections of rat brain was studied by a quantitative autoradiographic technique. Binding sites for this specific neuronal 5‐hydroxytryptamine (5‐HT) uptake inhibitor are concentrated in areas rich in 5‐HT neuronal cell bodies, fibers, and synaptic terminals. One of the most interesting features of this regional distribution is the very high density of these sites found in the dorsal raphe, substantia nigra, ventral tegmental area, and locus ceruleus. Components of the visual system also show pronounced labelling with [3H]indalpine. The finding that limbic structures are strongly labelled by this drug may be related to the antidepressant activity of indalpine. The anatomical distribution of binding sites demonstrated is Consistent with the specific labelling of 5‐HT neurons by [3H]indalpine and confirms previous studies carried out with another 5‐HT uptake inhibitor, [3H]imipramine.
We employed the 14C-deoxyglucose autoradiographic method to map the activity in the cerebellar co... more We employed the 14C-deoxyglucose autoradiographic method to map the activity in the cerebellar cortex of rhesus monkeys that performed forelimb movements either in the light or in the dark and of monkeys that observed forelimb movements executed by a human experimenter. The execution of forelimb movements, both in the light and in the dark, activated the forelimb representations in the cerebellar hemispheric extensions of 1) vermian lobules IV–VI and 2) vermian lobule VIIIB, ipsilaterally to the moving forelimb. Activations in the former forelimb representation involved both a paravermal and a lateral hemispheric region. Also, Crus II posterior in the ansiform lobule (the hemispheric expansion of lobule VIIB) was activated bilaterally by execution of movements in the light but not in the dark. Action observation activated the lateral-most region of the forelimb representation in the lateral hemispheric extension of vermian lobules IV–VI, as well as the crus II posterior, bilaterally...
Motor cognition is related to the planning and generation of actions as well as to the recognitio... more Motor cognition is related to the planning and generation of actions as well as to the recognition and imagination of motor acts. Recently, there is evidence that the motor system participates not only in overt actions but also in mental processes supporting covert actions. Within this framework, we have investigated the cortical areas engaged in execution, observation, and imagination of the same action, by the use of the high resolution quantitative 14C-deoxyglucose method in monkeys and by fMRI in humans, throughout the entire primate brain. Our data demonstrated that observing or imagining an action excites virtually the same sensory-motor cortical network which supports execution of that same action. In general agreement with the results of five relevant meta-analyses that we discuss extensively, our results imply mental practice, i.e. internal rehearsal of the action including movements and their sensory effects. We suggest that we actively perceive and imagine actions by selecting and running off-line restored sensory-motor memories, by mentally simulating the actions. We provide empirical evidence that mental simulation of actions underlies motor cognition, and conceptual representations are grounded in sensory-motor codes. Motor cognition may, therefore, be embodied and modal. Finally, we consider questions regarding agency attribution and the possible causal or epiphenomenal role the involved sensory-motor network could play in motor cognition.
The alterations in local metabolic activity of several anatomically distinct brain areas were inv... more The alterations in local metabolic activity of several anatomically distinct brain areas were investigated by means of the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose method in awake rats during unilateral electrical stimulation of the subthalamic nucleus (STH). Unilateral electrical stimulation of the STH induced local metabolic activation (by 70% as compared with the control group), as well as distal metabolic activations in the substantia nigra reticulata (by 34%), globus pallidus (by 19%), entopeduncular nucleus (by 18%), deep layers of the superior colliculi (by 15%), and parafascicular thalamic nucleus (by 18%), ipsilaterally to the stimulated side. The ventrolateral motor thalamic nucleus as well as the limbic components, posterior cingulate cortex, and anteroventral thalamic nucleus displayed bilateral metabolic activations (by 20–28%). These results indicate that, in addition to its known ipsilateral motor connections, each STH is functionally related to the limb...
The energy metabolism of 74 anatomically discrete central nervous structures was investigated by ... more The energy metabolism of 74 anatomically discrete central nervous structures was investigated by means of the autoradiographic 2-deoxy-D-(1-14C)glucose method (14C-DG) in conscious awake, as well as in halothane-anesthetized rats, following unilateral substantia nigra (SN) electrical stimulation. All the basal ganglia structures displayed bilateral metabolic activation in conscious animals, with only the contralateral subthalamic nucleus being unaffected. In anesthetized rats only the SN reticulata, globus pallidus, and subthalamic nucleus were affected ipsilaterally whereas anesthesia masked the effects of SN stimulation in SN compacta and striatum ipsilaterally, as well as within all the above structures contralaterally. The entopeduncular nucleus was bilaterally activated no matter the state of consciousness. Unilateral SN stimulation also increased glucose utilization within several thalamic regions (ventromedial, ventrolateral, ventroanterior, intralaminar, ventrobasal, and mediodorsal nuclei), the habenular complex, a few mesencephalic, brainstem (locus coeruleus and dorsal raphe) and cerebellar structures, mostly bilaterally and independently of the state of consciousness. Some of the factors suggested to be responsible for the masking effects of halothane-anesthesia on the metabolic activations elicited by unilateral SN stimulation are the following: (1) absence of movements in anesthetized rats, (2) halothane-induced depression of polysynaptic pathways mostly mediated through the thalamus, and (3) the stimulatory effect of halothane-anesthesia itself on metabolic activity in both parts of the SN.
A novel antimuscarinic agent, pirenzepine, has been proposed to distinguish at least two subtypes... more A novel antimuscarinic agent, pirenzepine, has been proposed to distinguish at least two subtypes of muscarinic receptor. M1 receptors have been designated as those displaying a high affinity for pirenzepine. Both functional and binding studies have revealed a prevalence of M1 receptors in sympathetic ganglia while autonomic effector tissues have only low densities of M1 receptors. In the present study, in vitro autoradiographic procedures have been used to localize specifically high affinity binding sites for pirenzepine (M1 receptors) in sections of guinea-pig ileum, rat superior cervical ganglion and rat submaxillary gland. The overall localization of muscarinic receptors was also studied using the non-selective antagonist, [3H]N-methylscopolamine. The highest densities of M1 receptors were found in superior cervical ganglion, sympathetic nerve bundles, myenteric ganglia and mucous secreting cells of the submaxillary gland, while lower densities were found in smooth muscle and serous secreting cells of the submaxillary gland. No area found to possess muscarinic receptors was devoid of M1 receptors.
The [3H]indalpine binding sites have been characterized in slide-mounted cat brain sections. This... more The [3H]indalpine binding sites have been characterized in slide-mounted cat brain sections. This inhibitor of 5-HT reuptake binds with a very high affinity to sites which have the pharmacological properties of the serotonin carrier. These sites can, however, be differentiated from the [3H]imipramine binding sites by their Na+ dependency and competitive inhibition by serotonin. Quantitative autoradiographic studies demonstrate that indalpine binding sites are localized in structures rich in serotonergic neurons. The widespread distribution of indalpine binding sites in limbic and associative areas is consisted with its well characterized antidepressant activity in human.
: The binding of [3H]indalpine {4‐[2‐(3‐indolyl)]ethyl piperidine} to slide‐mounted sections of r... more : The binding of [3H]indalpine {4‐[2‐(3‐indolyl)]ethyl piperidine} to slide‐mounted sections of rat brain has been characterized. This 5‐hydroxytryptamine (5‐HT) uptake blocker binds to sections with high affinity (KD∼ 1 nM). The binding is saturable, and can be displaced by the addition of clomipramine (1 μM). Other drugs inhibiting the uptake of 5‐HT also have the capacity to inhibit the binding of [3H]indalpine. A significant correlation (r = 0.86) was found between the capacity of these compounds to inhibit the uptake of 5‐HT and their potencies as inhibitors of [3H]indalpine binding. Binding was Na+‐ and Cl−dependent and was inhibited competitively by 5‐HT. Furthermore, electrolytic lesions of the dorsal raphe or medial forebrain bundle, which cause a degeneration of 5‐HT cell bodies and fibers, respectively, resulted in a 30–40% reduction in the binding of [3H]indalpine. [3H]Indalpine binds to the 5‐HT uptake recognition sites in a different manner from imipraminelike compounds.
: The localization of binding sites for [3H]indalpine to sections of rat brain was studied by a q... more : The localization of binding sites for [3H]indalpine to sections of rat brain was studied by a quantitative autoradiographic technique. Binding sites for this specific neuronal 5‐hydroxytryptamine (5‐HT) uptake inhibitor are concentrated in areas rich in 5‐HT neuronal cell bodies, fibers, and synaptic terminals. One of the most interesting features of this regional distribution is the very high density of these sites found in the dorsal raphe, substantia nigra, ventral tegmental area, and locus ceruleus. Components of the visual system also show pronounced labelling with [3H]indalpine. The finding that limbic structures are strongly labelled by this drug may be related to the antidepressant activity of indalpine. The anatomical distribution of binding sites demonstrated is Consistent with the specific labelling of 5‐HT neurons by [3H]indalpine and confirms previous studies carried out with another 5‐HT uptake inhibitor, [3H]imipramine.
We employed the 14C-deoxyglucose autoradiographic method to map the activity in the cerebellar co... more We employed the 14C-deoxyglucose autoradiographic method to map the activity in the cerebellar cortex of rhesus monkeys that performed forelimb movements either in the light or in the dark and of monkeys that observed forelimb movements executed by a human experimenter. The execution of forelimb movements, both in the light and in the dark, activated the forelimb representations in the cerebellar hemispheric extensions of 1) vermian lobules IV–VI and 2) vermian lobule VIIIB, ipsilaterally to the moving forelimb. Activations in the former forelimb representation involved both a paravermal and a lateral hemispheric region. Also, Crus II posterior in the ansiform lobule (the hemispheric expansion of lobule VIIB) was activated bilaterally by execution of movements in the light but not in the dark. Action observation activated the lateral-most region of the forelimb representation in the lateral hemispheric extension of vermian lobules IV–VI, as well as the crus II posterior, bilaterally...
Motor cognition is related to the planning and generation of actions as well as to the recognitio... more Motor cognition is related to the planning and generation of actions as well as to the recognition and imagination of motor acts. Recently, there is evidence that the motor system participates not only in overt actions but also in mental processes supporting covert actions. Within this framework, we have investigated the cortical areas engaged in execution, observation, and imagination of the same action, by the use of the high resolution quantitative 14C-deoxyglucose method in monkeys and by fMRI in humans, throughout the entire primate brain. Our data demonstrated that observing or imagining an action excites virtually the same sensory-motor cortical network which supports execution of that same action. In general agreement with the results of five relevant meta-analyses that we discuss extensively, our results imply mental practice, i.e. internal rehearsal of the action including movements and their sensory effects. We suggest that we actively perceive and imagine actions by selecting and running off-line restored sensory-motor memories, by mentally simulating the actions. We provide empirical evidence that mental simulation of actions underlies motor cognition, and conceptual representations are grounded in sensory-motor codes. Motor cognition may, therefore, be embodied and modal. Finally, we consider questions regarding agency attribution and the possible causal or epiphenomenal role the involved sensory-motor network could play in motor cognition.
The alterations in local metabolic activity of several anatomically distinct brain areas were inv... more The alterations in local metabolic activity of several anatomically distinct brain areas were investigated by means of the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose method in awake rats during unilateral electrical stimulation of the subthalamic nucleus (STH). Unilateral electrical stimulation of the STH induced local metabolic activation (by 70% as compared with the control group), as well as distal metabolic activations in the substantia nigra reticulata (by 34%), globus pallidus (by 19%), entopeduncular nucleus (by 18%), deep layers of the superior colliculi (by 15%), and parafascicular thalamic nucleus (by 18%), ipsilaterally to the stimulated side. The ventrolateral motor thalamic nucleus as well as the limbic components, posterior cingulate cortex, and anteroventral thalamic nucleus displayed bilateral metabolic activations (by 20–28%). These results indicate that, in addition to its known ipsilateral motor connections, each STH is functionally related to the limb...
The energy metabolism of 74 anatomically discrete central nervous structures was investigated by ... more The energy metabolism of 74 anatomically discrete central nervous structures was investigated by means of the autoradiographic 2-deoxy-D-(1-14C)glucose method (14C-DG) in conscious awake, as well as in halothane-anesthetized rats, following unilateral substantia nigra (SN) electrical stimulation. All the basal ganglia structures displayed bilateral metabolic activation in conscious animals, with only the contralateral subthalamic nucleus being unaffected. In anesthetized rats only the SN reticulata, globus pallidus, and subthalamic nucleus were affected ipsilaterally whereas anesthesia masked the effects of SN stimulation in SN compacta and striatum ipsilaterally, as well as within all the above structures contralaterally. The entopeduncular nucleus was bilaterally activated no matter the state of consciousness. Unilateral SN stimulation also increased glucose utilization within several thalamic regions (ventromedial, ventrolateral, ventroanterior, intralaminar, ventrobasal, and mediodorsal nuclei), the habenular complex, a few mesencephalic, brainstem (locus coeruleus and dorsal raphe) and cerebellar structures, mostly bilaterally and independently of the state of consciousness. Some of the factors suggested to be responsible for the masking effects of halothane-anesthesia on the metabolic activations elicited by unilateral SN stimulation are the following: (1) absence of movements in anesthetized rats, (2) halothane-induced depression of polysynaptic pathways mostly mediated through the thalamus, and (3) the stimulatory effect of halothane-anesthesia itself on metabolic activity in both parts of the SN.
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Papers by Helen Savaki