Electroencephalography and clinical neurophysiology, 1998
Acoustic P300 was recorded from Fz, Cz and Pz by means of an 'odd-ball' paradigm in 44 no... more Acoustic P300 was recorded from Fz, Cz and Pz by means of an 'odd-ball' paradigm in 44 non-demented de novo Parkinson's disease patients (PD) or PD patients under treatment withdrawal, and in 31 age-matched normal subjects, to evaluate whether a P300 latency increase was present in PD patients. The influence of age and disease stage on latency was successively verified by subgrouping PD patients according to different age ('young' and 'old') and disease stage ('early' or 'advanced'). PD patient data were compared to data of normal subjects subgrouped into 'young' and 'old' or, to eliminate the age-dependent shift of latency, this latter was adjusted to 60 years in all the examined subjects. A significant increase of latency has been found in Fz and Cz in the 'old' group of PD patients (n = 23) but not in the 'young' group (n = 21) utilising both methods. Moreover, a significant latency increase was also pres...
Journal of neural transmission. Supplementum, 2006
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) pat... more Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) patients augments STN-driven excitation of the internal globus pallidus (GPi). However, other DBS-induced changes are largely unknown. Here we report the biochemical effects of STN-DBS in two basal ganglia stations (putamen--PUT--and GPi) and in a thalamic relay nucleus, the anteroventral thalamus (VA). In six advanced PD patients undergoing surgery, microdialysis samples were collected from GPi, PUT and VA before, during and after one hour of STN-DBS. cGMP was measured in the GPi and PUT as an index of glutamatergic transmission, whereas GABA was measured in the VA. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in the VA (-25%). Simultaneously, cGMP extracellular concentrations were enhanced in the PUT (+200%) and GPi (+481%). DBS differentially affects fibers crossing the STN area: it activates the STN-GPi pathway while inhibitin...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2002
Cannabinoid receptors and their endogenous ligands have been recently identified in the brain as ... more Cannabinoid receptors and their endogenous ligands have been recently identified in the brain as potent inhibitors of neurotransmitter release. Here we show that, in a rat model of Parkinson's disease induced by unilateral nigral lesion with 6-hydroxydopamine (6-OHDA), the striatal levels of anandamide, but not that of the other endocannabinoid 2-arachidonoylglycerol, were increased. Moreover, we observed a decreased activity of the anandamide membrane transporter (AMT) and of the anandamide hydrolase [fatty acid amide hydrolase (FAAH)], whereas the binding of anandamide to cannabinoid receptors was unaffected. Spontaneous glutamatergic activity recorded from striatal spiny neurons was higher in 6-OHDA-lesioned rats. Inhibition of AMT by N-(4-hydroxyphenyl)-arachidonoylamide (AM-404) or by VDM11, or stimulation of the cannabinoid CB1 receptor by HU-210 reduced glutamatergic spontaneous activity in both naive and 6-OHDA-lesioned animals to a similar extent. Conversely, the FAAH i...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2002
Striatal cholinergic interneurons were recorded from a rat slice preparation. Synaptic potentials... more Striatal cholinergic interneurons were recorded from a rat slice preparation. Synaptic potentials evoked by intrastriatal stimulation revealed three distinct components: a glutamatergic EPSP, a GABA(A)-mediated depolarizing potential, and an acetylcholine (ACh)-mediated IPSP. The responses to group II metabotropic glutamate (mGlu) receptor activation were investigated on the isolated components of the synaptic potentials. Each pharmacologically isolated component was reversibly reduced by bath-applied LY379268 and ((2S,1'R,2'R,3'R)-2-(2,3-dicarboxylcyclopropyl)-glycine, group II agonists. In an attempt to define the relevance of group II mGlu receptor activation on cholinergic transmission, we focused on the inhibitory effect on the IPSP, which was mimicked and occluded by omega-agatoxin IVA (omega-Aga-IVA), suggesting a modulation on P-type high-voltage-activated calcium channels. Spontaneous calcium-dependent plateau-potentials (PPs) were recorded with cesium-filled el...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2001
Conflicting data have been collected so far on the action of nitric oxide (NO) on cholinergic int... more Conflicting data have been collected so far on the action of nitric oxide (NO) on cholinergic interneurons of the striatum. In the present in vitro electrophysiological study, we reported that intracellularly recorded striatal cholinergic interneurons are excited by both hydroxylamine and S-nitroso-N-acetylpenicillamine, two NO donors. This excitation persisted unchanged in the presence of glutamate, dopamine, and substance P receptor antagonists as well as after blockade of tetrodotoxin (TTX)- and calcium channel-sensitive transmitter release, suggesting that NO produces its effects by modulating directly resting ion conductances in the somatodendritic region of striatal cholinergic cells. The depolarizing effect of hydroxylamine was greatly reduced by lowering external concentrations of sodium ions (from 126 to 38 mm) and did not reverse polarity in the voltage range from -120 to -40 mV. The sodium transporter blockers bepridil and 3',4'-dichlorobenzamil were conversely in...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2000
A complex chain of intracellular signaling events, critically important in motor control, is acti... more A complex chain of intracellular signaling events, critically important in motor control, is activated by the stimulation of D1-like dopamine (DA) receptors in striatal neurons. At corticostriatal synapses on medium spiny neurons, we provide evidence that the D1-like receptor-dependent activation of DA and cyclic adenosine 3',5' monophosphate-regulated phosphoprotein 32 kDa is a crucial step for the induction of both long-term depression (LTD) and long-term potentiation (LTP), two opposing forms of synaptic plasticity. In addition, formation of LTD and LTP requires the activation of protein kinase G and protein kinase A, respectively, in striatal projection neurons. These kinases appear to be stimulated by the activation of D1-like receptors in distinct neuronal populations.
The pathogenesis of the alterations in motor response that complicate levodopa therapy of Parkins... more The pathogenesis of the alterations in motor response that complicate levodopa therapy of Parkinson's disease remains obscure. Several experimental and clinical observations strongly suggest that changes in striatal activity may be crucial for this physiopathological condition. Accordingly, it has been postulated that dyskinesia might be due to abnormal activity of the corticostriatal pathway. Here, we review the physiological and pharmacological mechanisms underlying glutamatergic regulation of striatal neurons by the corticostriatal projection. In particular, we discuss the role of both (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors in the control of the short- and long-term efficacy of corticostriatal transmission. Indeed, repetitive cortical activation can generate either long-term depression or long-term potentiation (LTP) at corticostriatal synapses depending on the subtype of glutamate receptor acti...
Two classes of genes were identified in three Gramineae (maize, rice, barley) and six dicots (Ara... more Two classes of genes were identified in three Gramineae (maize, rice, barley) and six dicots (Arabidopsis, soybean, pea, tobacco, tomato, potato). One class, the GC-rich class, contained genes with no, or few, short introns. In contrast, the GC-poor class contained genes with numerous, long introns. The similarity of the properties of each class, as present in the genomes of maize and Arabidopsis, is particularly remarkable in view of the fact that these plants exhibit large differences in genome size, average intron size, and DNA base composition. The functional relevance of the two classes of genes is stressed by (1) the conservation in homologous genes from maize and Arabidopsis not only of the number of introns and of their positions, but also of the relative size of concatenated introns; and (2) the existence of two similar classes of genes in vertebrates; interestingly, the differences in intron sizes and numbers in genes from the GC-poor and GC-rich classes are much more stri...
We studied the role of endogenous acetylcholine (Ach) in corticostriatal long-term potentiation (... more We studied the role of endogenous acetylcholine (Ach) in corticostriatal long-term potentiation (LTP). The muscarinic receptor antagonists scopolamine and pirenzepine fully prevented the induction of LTP suggesting that the activation of M1-like muscarinic receptors is a crucial event in the conditioning phase of this form of synaptic plasticity.
Electroencephalography and clinical neurophysiology, 1998
Systemic decrease of dopaminergic cells, such as in Parkinson's disease may produce visual al... more Systemic decrease of dopaminergic cells, such as in Parkinson's disease may produce visual alterations in humans. In order to show possible pattern electroretinogram (PERG) spatial tuning function (STF) alterations due to impaired dopaminergic transmission in humans, we studied a group of Parkinson's disease patients before and during treatment with the dopamine precursor, levodopa, and compared their performances with those of an age-matched control group. Moreover, in order to exclude the possible involvement of motor disabilities to produce PERG alterations, we also investigated PERG responses in post-traumatic parkinsonian patients who exhibited motor abnormalities as a consequence of focal lesions of basal ganglia, in the absence of systemic dopaminergic degeneration. Our results showed a clear decrease of PERG responses in Parkinson's disease patients particularly at medium spatial frequency range (2.7-4.0 cycles/degree) with a substantial preservation of responses...
Dopamine plays a key role in the control of motor and cognitive functions through the interaction... more Dopamine plays a key role in the control of motor and cognitive functions through the interaction with membrane receptors. Dopamine elicits its physiological effect by interacting with receptors that belong to the seven transmembrane domain G-protein-coupled receptors family. Pharmacological and structural analyses have allowed the division of these receptors into two classes: the D1- and D2-like receptors. The D1-like subfamily comprises D1 and D5 while the D2-like is formed by D2, D3 and D4. Dopaminergic neurons arise from the ventral tegmental area and the substantia nigra. These neurons give rise to four dopaminergic pathways: the nigrostriatal, the mesolimbic, the mesocortical and tuberoinfundibular pathways. These pathways are involved in the control of movement, learning, motivation reward and hormone synthesis and release. Dysfunction in these pathways leads to neurological, psychiatric and endocrine disorders. Indeed, degeneration of the nigrostriatal pathway leads to Parki...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1997
Dopamine D2 receptors (D2Rs) are of crucial importance in the striatal processing of motor inform... more Dopamine D2 receptors (D2Rs) are of crucial importance in the striatal processing of motor information received from the cortex. Disruption of the D2R gene function in mice results in a severe locomotor impairment. This phenotype has analogies with Parkinson's disease symptoms. D2R-null mice were used to investigate the role of this receptor in the generation of striatal synaptic plasticity. Tetanic stimulation of corticostriatal fibers produced long-term depression (LTD) of EPSPs in slices from wild-type (WT) mice. Strikingly, recordings from D2R-null mice showed the converse: long-term potentiation (LTP). This LTP, unlike LTD, was blocked by an NMDA receptor antagonist. In magnesium-free medium, LTP was also revealed in WT mice and found to be enhanced by L-sulpiride, a D2R antagonist, whereas it was reversed into LTD by LY 17555, a D2R agonist. In D2R-null mice this modulation was lost. Thus, our study indicates that D2Rs play a key role in mechanisms underlying the direction...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1997
We have studied the electrophysiological effects of glucose deprivation on morphologically identi... more We have studied the electrophysiological effects of glucose deprivation on morphologically identified striatal neurons recorded from a corticostriatal slice preparation. The large majority of the recorded cells were spiny neurons and responded to aglycemia with a slow membrane depolarization coupled with a reduction of the input resistance. In voltage-clamp experiments aglycemia caused an inward current. This current was associated with a conductance increase and reversed at -40 mV. The aglycemia-induced membrane depolarization was not affected by tetrodotoxin (TTX) or 6-cyano-7-nitroquinoxaline-2,3-dione plus aminophosphonovalerate, antagonists acting respectively on AMPA and NMDA glutamate receptors. Also, the intracellular injection of bis(2-aminophenoxy)ethane-N,N, N',N'-tetra-acetic acid, a calcium (Ca2+) chelator, and low Ca2+/high Mg2+-containing solutions failed to reduce this phenomenon. Conversely, it was reduced by lowering external sodium (Na+) concentration. A m...
Recombinant plasmids were made containing cDNAs synthesized on hamster mRNAs coding for cytoskele... more Recombinant plasmids were made containing cDNAs synthesized on hamster mRNAs coding for cytoskeletal (beta- or gamma-) actins and for vimentin. Hybridization of the actin probe on restriction digests of one avian and five mammalian DNAs yielded multiple bands; the vimentin probe revealed only one band (accompanied by 2-3 faint bands in some DNAs). The results obtained with the vimentin probe indicate that the corresponding coding sequences: (a) are highly conserved in warm-blooded vertebrates like the actin sequences; (b) have strongly diverged from those coding for other intermediate filament proteins, since hybridization of the vimentin probe does not lead to a diagnostic multiband pattern; and (c) most likely contribute to single gene, in contrast to the sequences coding for other cytoskeletal proteins. Hybridization of the probes on mRNAs from the different sources used showed that the non-coding sequences of both vimentin and actin genes are conserved in length.
The localization of the epileptogenic focus relies on different factors. In patients with partial... more The localization of the epileptogenic focus relies on different factors. In patients with partial seizures, asymmetries in EEG background activity were measured by a statistical evaluation of spectral data. Neurophysiological results were compared with neuropsychological findings and MRI. Fifteen of 22 patients showed asymmetries in EEG background activity. The most prominent abnormality was a statistically significant increase of slow activity observed in 59% of cases. Delta asymmetry coincided with the site of lesions, evidenced by MRI, in 83% of patients; with the site of decreased beta activity in 60% and with the maximum level of spiking activity in 58% of cases. Neuropsychological tests showed a lateralization of the hemispheric function which coincided with delta asymmetry in 33% of patients. These results suggest that the EEG background activity, when compared with other parameters, may represent a useful method in lateralizing the epileptogenic focus.
... RF are organized into higher order patterns within the nucleus, and studies on fixed cells in... more ... RF are organized into higher order patterns within the nucleus, and studies on fixed cells indicate that there are characteristic patterns for different stages of S phase (Nakayasu and Berezney 1989; O'Keefe et al. 1992; Ferreira et al. 1997). ...
Electroencephalography and clinical neurophysiology, 1998
Acoustic P300 was recorded from Fz, Cz and Pz by means of an 'odd-ball' paradigm in 44 no... more Acoustic P300 was recorded from Fz, Cz and Pz by means of an 'odd-ball' paradigm in 44 non-demented de novo Parkinson's disease patients (PD) or PD patients under treatment withdrawal, and in 31 age-matched normal subjects, to evaluate whether a P300 latency increase was present in PD patients. The influence of age and disease stage on latency was successively verified by subgrouping PD patients according to different age ('young' and 'old') and disease stage ('early' or 'advanced'). PD patient data were compared to data of normal subjects subgrouped into 'young' and 'old' or, to eliminate the age-dependent shift of latency, this latter was adjusted to 60 years in all the examined subjects. A significant increase of latency has been found in Fz and Cz in the 'old' group of PD patients (n = 23) but not in the 'young' group (n = 21) utilising both methods. Moreover, a significant latency increase was also pres...
Journal of neural transmission. Supplementum, 2006
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) pat... more Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) patients augments STN-driven excitation of the internal globus pallidus (GPi). However, other DBS-induced changes are largely unknown. Here we report the biochemical effects of STN-DBS in two basal ganglia stations (putamen--PUT--and GPi) and in a thalamic relay nucleus, the anteroventral thalamus (VA). In six advanced PD patients undergoing surgery, microdialysis samples were collected from GPi, PUT and VA before, during and after one hour of STN-DBS. cGMP was measured in the GPi and PUT as an index of glutamatergic transmission, whereas GABA was measured in the VA. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in the VA (-25%). Simultaneously, cGMP extracellular concentrations were enhanced in the PUT (+200%) and GPi (+481%). DBS differentially affects fibers crossing the STN area: it activates the STN-GPi pathway while inhibitin...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2002
Cannabinoid receptors and their endogenous ligands have been recently identified in the brain as ... more Cannabinoid receptors and their endogenous ligands have been recently identified in the brain as potent inhibitors of neurotransmitter release. Here we show that, in a rat model of Parkinson's disease induced by unilateral nigral lesion with 6-hydroxydopamine (6-OHDA), the striatal levels of anandamide, but not that of the other endocannabinoid 2-arachidonoylglycerol, were increased. Moreover, we observed a decreased activity of the anandamide membrane transporter (AMT) and of the anandamide hydrolase [fatty acid amide hydrolase (FAAH)], whereas the binding of anandamide to cannabinoid receptors was unaffected. Spontaneous glutamatergic activity recorded from striatal spiny neurons was higher in 6-OHDA-lesioned rats. Inhibition of AMT by N-(4-hydroxyphenyl)-arachidonoylamide (AM-404) or by VDM11, or stimulation of the cannabinoid CB1 receptor by HU-210 reduced glutamatergic spontaneous activity in both naive and 6-OHDA-lesioned animals to a similar extent. Conversely, the FAAH i...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2002
Striatal cholinergic interneurons were recorded from a rat slice preparation. Synaptic potentials... more Striatal cholinergic interneurons were recorded from a rat slice preparation. Synaptic potentials evoked by intrastriatal stimulation revealed three distinct components: a glutamatergic EPSP, a GABA(A)-mediated depolarizing potential, and an acetylcholine (ACh)-mediated IPSP. The responses to group II metabotropic glutamate (mGlu) receptor activation were investigated on the isolated components of the synaptic potentials. Each pharmacologically isolated component was reversibly reduced by bath-applied LY379268 and ((2S,1'R,2'R,3'R)-2-(2,3-dicarboxylcyclopropyl)-glycine, group II agonists. In an attempt to define the relevance of group II mGlu receptor activation on cholinergic transmission, we focused on the inhibitory effect on the IPSP, which was mimicked and occluded by omega-agatoxin IVA (omega-Aga-IVA), suggesting a modulation on P-type high-voltage-activated calcium channels. Spontaneous calcium-dependent plateau-potentials (PPs) were recorded with cesium-filled el...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2001
Conflicting data have been collected so far on the action of nitric oxide (NO) on cholinergic int... more Conflicting data have been collected so far on the action of nitric oxide (NO) on cholinergic interneurons of the striatum. In the present in vitro electrophysiological study, we reported that intracellularly recorded striatal cholinergic interneurons are excited by both hydroxylamine and S-nitroso-N-acetylpenicillamine, two NO donors. This excitation persisted unchanged in the presence of glutamate, dopamine, and substance P receptor antagonists as well as after blockade of tetrodotoxin (TTX)- and calcium channel-sensitive transmitter release, suggesting that NO produces its effects by modulating directly resting ion conductances in the somatodendritic region of striatal cholinergic cells. The depolarizing effect of hydroxylamine was greatly reduced by lowering external concentrations of sodium ions (from 126 to 38 mm) and did not reverse polarity in the voltage range from -120 to -40 mV. The sodium transporter blockers bepridil and 3',4'-dichlorobenzamil were conversely in...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2000
A complex chain of intracellular signaling events, critically important in motor control, is acti... more A complex chain of intracellular signaling events, critically important in motor control, is activated by the stimulation of D1-like dopamine (DA) receptors in striatal neurons. At corticostriatal synapses on medium spiny neurons, we provide evidence that the D1-like receptor-dependent activation of DA and cyclic adenosine 3',5' monophosphate-regulated phosphoprotein 32 kDa is a crucial step for the induction of both long-term depression (LTD) and long-term potentiation (LTP), two opposing forms of synaptic plasticity. In addition, formation of LTD and LTP requires the activation of protein kinase G and protein kinase A, respectively, in striatal projection neurons. These kinases appear to be stimulated by the activation of D1-like receptors in distinct neuronal populations.
The pathogenesis of the alterations in motor response that complicate levodopa therapy of Parkins... more The pathogenesis of the alterations in motor response that complicate levodopa therapy of Parkinson's disease remains obscure. Several experimental and clinical observations strongly suggest that changes in striatal activity may be crucial for this physiopathological condition. Accordingly, it has been postulated that dyskinesia might be due to abnormal activity of the corticostriatal pathway. Here, we review the physiological and pharmacological mechanisms underlying glutamatergic regulation of striatal neurons by the corticostriatal projection. In particular, we discuss the role of both (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors in the control of the short- and long-term efficacy of corticostriatal transmission. Indeed, repetitive cortical activation can generate either long-term depression or long-term potentiation (LTP) at corticostriatal synapses depending on the subtype of glutamate receptor acti...
Two classes of genes were identified in three Gramineae (maize, rice, barley) and six dicots (Ara... more Two classes of genes were identified in three Gramineae (maize, rice, barley) and six dicots (Arabidopsis, soybean, pea, tobacco, tomato, potato). One class, the GC-rich class, contained genes with no, or few, short introns. In contrast, the GC-poor class contained genes with numerous, long introns. The similarity of the properties of each class, as present in the genomes of maize and Arabidopsis, is particularly remarkable in view of the fact that these plants exhibit large differences in genome size, average intron size, and DNA base composition. The functional relevance of the two classes of genes is stressed by (1) the conservation in homologous genes from maize and Arabidopsis not only of the number of introns and of their positions, but also of the relative size of concatenated introns; and (2) the existence of two similar classes of genes in vertebrates; interestingly, the differences in intron sizes and numbers in genes from the GC-poor and GC-rich classes are much more stri...
We studied the role of endogenous acetylcholine (Ach) in corticostriatal long-term potentiation (... more We studied the role of endogenous acetylcholine (Ach) in corticostriatal long-term potentiation (LTP). The muscarinic receptor antagonists scopolamine and pirenzepine fully prevented the induction of LTP suggesting that the activation of M1-like muscarinic receptors is a crucial event in the conditioning phase of this form of synaptic plasticity.
Electroencephalography and clinical neurophysiology, 1998
Systemic decrease of dopaminergic cells, such as in Parkinson's disease may produce visual al... more Systemic decrease of dopaminergic cells, such as in Parkinson's disease may produce visual alterations in humans. In order to show possible pattern electroretinogram (PERG) spatial tuning function (STF) alterations due to impaired dopaminergic transmission in humans, we studied a group of Parkinson's disease patients before and during treatment with the dopamine precursor, levodopa, and compared their performances with those of an age-matched control group. Moreover, in order to exclude the possible involvement of motor disabilities to produce PERG alterations, we also investigated PERG responses in post-traumatic parkinsonian patients who exhibited motor abnormalities as a consequence of focal lesions of basal ganglia, in the absence of systemic dopaminergic degeneration. Our results showed a clear decrease of PERG responses in Parkinson's disease patients particularly at medium spatial frequency range (2.7-4.0 cycles/degree) with a substantial preservation of responses...
Dopamine plays a key role in the control of motor and cognitive functions through the interaction... more Dopamine plays a key role in the control of motor and cognitive functions through the interaction with membrane receptors. Dopamine elicits its physiological effect by interacting with receptors that belong to the seven transmembrane domain G-protein-coupled receptors family. Pharmacological and structural analyses have allowed the division of these receptors into two classes: the D1- and D2-like receptors. The D1-like subfamily comprises D1 and D5 while the D2-like is formed by D2, D3 and D4. Dopaminergic neurons arise from the ventral tegmental area and the substantia nigra. These neurons give rise to four dopaminergic pathways: the nigrostriatal, the mesolimbic, the mesocortical and tuberoinfundibular pathways. These pathways are involved in the control of movement, learning, motivation reward and hormone synthesis and release. Dysfunction in these pathways leads to neurological, psychiatric and endocrine disorders. Indeed, degeneration of the nigrostriatal pathway leads to Parki...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1997
Dopamine D2 receptors (D2Rs) are of crucial importance in the striatal processing of motor inform... more Dopamine D2 receptors (D2Rs) are of crucial importance in the striatal processing of motor information received from the cortex. Disruption of the D2R gene function in mice results in a severe locomotor impairment. This phenotype has analogies with Parkinson's disease symptoms. D2R-null mice were used to investigate the role of this receptor in the generation of striatal synaptic plasticity. Tetanic stimulation of corticostriatal fibers produced long-term depression (LTD) of EPSPs in slices from wild-type (WT) mice. Strikingly, recordings from D2R-null mice showed the converse: long-term potentiation (LTP). This LTP, unlike LTD, was blocked by an NMDA receptor antagonist. In magnesium-free medium, LTP was also revealed in WT mice and found to be enhanced by L-sulpiride, a D2R antagonist, whereas it was reversed into LTD by LY 17555, a D2R agonist. In D2R-null mice this modulation was lost. Thus, our study indicates that D2Rs play a key role in mechanisms underlying the direction...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1997
We have studied the electrophysiological effects of glucose deprivation on morphologically identi... more We have studied the electrophysiological effects of glucose deprivation on morphologically identified striatal neurons recorded from a corticostriatal slice preparation. The large majority of the recorded cells were spiny neurons and responded to aglycemia with a slow membrane depolarization coupled with a reduction of the input resistance. In voltage-clamp experiments aglycemia caused an inward current. This current was associated with a conductance increase and reversed at -40 mV. The aglycemia-induced membrane depolarization was not affected by tetrodotoxin (TTX) or 6-cyano-7-nitroquinoxaline-2,3-dione plus aminophosphonovalerate, antagonists acting respectively on AMPA and NMDA glutamate receptors. Also, the intracellular injection of bis(2-aminophenoxy)ethane-N,N, N',N'-tetra-acetic acid, a calcium (Ca2+) chelator, and low Ca2+/high Mg2+-containing solutions failed to reduce this phenomenon. Conversely, it was reduced by lowering external sodium (Na+) concentration. A m...
Recombinant plasmids were made containing cDNAs synthesized on hamster mRNAs coding for cytoskele... more Recombinant plasmids were made containing cDNAs synthesized on hamster mRNAs coding for cytoskeletal (beta- or gamma-) actins and for vimentin. Hybridization of the actin probe on restriction digests of one avian and five mammalian DNAs yielded multiple bands; the vimentin probe revealed only one band (accompanied by 2-3 faint bands in some DNAs). The results obtained with the vimentin probe indicate that the corresponding coding sequences: (a) are highly conserved in warm-blooded vertebrates like the actin sequences; (b) have strongly diverged from those coding for other intermediate filament proteins, since hybridization of the vimentin probe does not lead to a diagnostic multiband pattern; and (c) most likely contribute to single gene, in contrast to the sequences coding for other cytoskeletal proteins. Hybridization of the probes on mRNAs from the different sources used showed that the non-coding sequences of both vimentin and actin genes are conserved in length.
The localization of the epileptogenic focus relies on different factors. In patients with partial... more The localization of the epileptogenic focus relies on different factors. In patients with partial seizures, asymmetries in EEG background activity were measured by a statistical evaluation of spectral data. Neurophysiological results were compared with neuropsychological findings and MRI. Fifteen of 22 patients showed asymmetries in EEG background activity. The most prominent abnormality was a statistically significant increase of slow activity observed in 59% of cases. Delta asymmetry coincided with the site of lesions, evidenced by MRI, in 83% of patients; with the site of decreased beta activity in 60% and with the maximum level of spiking activity in 58% of cases. Neuropsychological tests showed a lateralization of the hemispheric function which coincided with delta asymmetry in 33% of patients. These results suggest that the EEG background activity, when compared with other parameters, may represent a useful method in lateralizing the epileptogenic focus.
... RF are organized into higher order patterns within the nucleus, and studies on fixed cells in... more ... RF are organized into higher order patterns within the nucleus, and studies on fixed cells indicate that there are characteristic patterns for different stages of S phase (Nakayasu and Berezney 1989; O'Keefe et al. 1992; Ferreira et al. 1997). ...
Uploads
Papers