Neuropeptide Y (NPY), an apparent neuromodulating neuropeptide, has been linked to dopamine systems and dopamine-related psychotic disorders. Because of this association, we determined and compared the effects of psychotomimetic drugs on extrapyramidal and limbic NPY systems. We observed that phencyclidine, methamphetamine (METH), (+)methylenedioxymethamphetamine (MDMA), and cocaine, but not (-)MDMA, similarly reduced the striatal content of NPY-like immunoreactivity from 54% (phencyclidine) to 74% [(+) MDMA] of control. The effects of METH on NPY levels in the nucleus accumbens, caudate nucleus, globus pallidus, and substantia nigra were characterized in greater detail. We observed that METH decreased NPY levels in specific regions of the nucleus accumbens and the caudate, but had no effect on NPY in the globus pallidus or the substantia nigra. The dopamine D1 receptor antagonist SCH-23390 blocked these effects of METH, suggesting that NPY levels throughout the nucleus accumbens and the caudate are regulated through D1 pathways. The D2 receptor antagonist eticlopride did not appear to alter the METH effect, but this was difficult to determine because eticlopride decreased NPY levels by itself. A single dose of METH was sufficient to lower NPY levels, in some, but not all, regions examined. The effects on NPY levels after multiple METH administrations were substantially greater and persisted up to 48 h after treatment; this suggests that synthesis of this neuropeptide may be suppressed even after the drug is gone. These findings suggest that NPY systems may contribute to the D1 receptor-mediated effects of the psychostimulants. (+info)
(2/970) Development of the temporal lobe in infants and children: analysis by MR-based volumetry.
BACKGROUND AND PURPOSE: Recent advances in data-processing techniques have allowed more accurate MR-based volumetric measurement than was possible in the past. The purpose of this study was to use this technique to evaluate the development of the temporal lobes in childhood. METHODS: The study group consisted of 42 subjects aged 3 weeks to 14 years (mean age, 5 years), all with normal findings on a routine MR study and none with a history of epilepsy. MR images were acquired on a 1.0-T system using a T1-weighted 3D ultrafast gradient-echo sequence. The volumes of the hippocampal formations and temporal lobes were measured by using a workstation, and the percentage of hippocampal formations in the temporal lobes was calculated. Myelination in the limbic system and related structures was also evaluated. RESULTS: The volume of the hippocampal formations increased sharply until the age of 2 years, and continued to increase slowly thereafter. However, the percentage of hippocampal formations in the temporal lobes showed a negative correlation with age. The hippocampal formations on the right side were larger than those on the left in 38 cases (91%), and the anterior temporal lobes on the right were larger than those on the left in 32 cases (76%). This right-left asymmetry of the hippocampal formations and anterior temporal lobes was observed from early infancy, and these differences were statistically significant. A longitudinal fasciculus of high signal intensity was seen in the white matter beneath the subiculum by about 3 months of age. CONCLUSION: MR-based volumetry established developmental characteristics of the temporal lobe, such as a hippocampal growth spurt, a growth difference between the hippocampal formation and the rest of the temporal lobe, and right-left asymmetry. Knowledge of these characteristics may aid in the understanding of hippocampal and temporal lobe abnormalities in children. (+info)
(3/970) Differential regulation of glucocorticoid receptor messenger RNA (GR-mRNA) by maternal deprivation in immature rat hypothalamus and limbic regions.
Maternal deprivation (MDep) of neonatal rats significantly influences the hypothalamic-pituitary-adrenal (HPA) axis. This study hypothesized that GR-mRNA modulation constituted an early, critical mechanism for the acute effects of MDep on neuroendocrine stress-responses. GR-mRNA hybridization signal in hippocampal CA1, hypothalamic paraventricular nucleus (PVN) and frontal cortex was significantly reduced immediately following 24 h MDep. In amygdala, cingulate cortex, PVN and CA1, apparent gender-dependent MDep effects on GR-mRNA expression were observed, without significant differences in absolute levels. Thus, rapid, region-specific MDep effects on GR-mRNA expression in HPA-regulating areas are shown, consistent with involvement of GR-expression in mechanisms of MDep influence on HPA tone. (+info)
(4/970) Involvement of the prelimbic-infralimbic areas of the rodent prefrontal cortex in behavioral flexibility for place and response learning.
The present experiments investigated the role of the prelimbic-infralimbic areas in behavioral flexibility using a place-response learning paradigm. All rats received a bilateral cannula implant aimed at the prelimbic-infralimbic areas. To examine the role of the prelimbic-infralimbic areas in shifting strategies, rats were tested on a place and a response discrimination in a cross-maze. Some rats were tested on the place version first followed by the response version. The procedure for the other rats was reversed. Infusions of 2% tetracaine into the prelimbic-infralimbic areas did not impair acquisition of the place or response discriminations. Prelimbic-infralimbic inactivation did impair learning when rats were switched from one discrimination to the other (cross-modal shift). To investigate the role of the prelimbic-infralimbic areas in intramodal shifts (reversal learning), one group of rats was tested on a place reversal and another group tested on a response reversal. Prelimbic-infralimbic inactivation did not impair place or response intramodal shifts. Some rats that completed testing on a particular version in the cross-modal and intramodal experiments were tested on the same version in a new room for 3 d. The transfer tests revealed that rats use a spatial strategy on the place version and an egocentric response strategy on the response version. Overall, these results suggest that the prelimbic-infralimbic areas are important for behavioral flexibility involving cross-modal but not intramodal shifts. (+info)
(5/970) The connectional organization of the cortico-thalamic system of the cat.
Data on connections between the areas of the cerebral cortex and nuclei of the thalamus are too complicated to analyse with naked intuition. Indeed, the complexity of connection data is one of the major challenges facing neuroanatomy. Recently, systematic methods have been developed and applied to the analysis of the connectivity in the cerebral cortex. These approaches have shed light on the gross organization of the cortical network, have made it possible to test systematically theories of cortical organization, and have guided new electrophysiological studies. This paper extends the approach to investigate the organization of the entire cortico-thalamic network. An extensive collation of connection tracing studies revealed approximately 1500 extrinsic connections between the cortical areas and thalamic nuclei of the cat cerebral hemisphere. Around 850 connections linked 53 cortical areas with each other, and around 650 connections linked the cortical areas with 42 thalamic nuclei. Non-metric multidimensional scaling, optimal set analysis and non-parametric cluster analysis were used to study global connectivity and the 'place' of individual structures within the overall scheme. Thalamic nuclei and cortical areas were in intimate connectional association. Connectivity defined four major thalamo-cortical systems. These included three broadly hierarchical sensory or sensory/motor systems (visual and auditory systems and a single system containing both somatosensory and motor structures). The highest stations of these sensory/motor systems were associated with a fourth processing system composed of prefrontal, cingulate, insular and parahippocampal cortex and associated thalamic nuclei (the 'fronto-limbic system'). The association between fronto-limbic and somato-motor systems was particularly close. (+info)
(6/970) A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer.
BACKGROUND: In patients with cancer, symptoms of limbic and brain-stem dysfunction may result from a paraneoplastic disorder. Paraneoplastic limbic or brain-stem encephalitis occurs more frequently with testicular cancer than with most other cancers. We sought antineuronal antibodies that might be used in a diagnostic test for this syndrome. METHODS: Immunohistochemical and immunoblotting techniques were used to detect serum and cerebrospinal fluid antibodies. Serologic screening of a complementary DNA library and Northern blotting were used to clone the target antigen and determine which tissues expressed it. RESULTS: Of 13 patients with testicular cancer and paraneoplastic limbic or brain-stem encephalitis (or both), 10 had antibodies in serum and cerebrospinal fluid against a 40-kd neuronal protein. These antibodies were used to clone a gene that we call Ma2, which codes for a protein (Ma2) that was recognized by serum from the 10 patients, but not by serum from 344 control subjects. Ma2 was selectively expressed by normal brain tissue and by the testicular tumors of the patients. Ma2 shares homology with Ma1, a "brain-testis-cancer" gene related to other paraneoplastic syndromes and tumors. CONCLUSIONS: The serum of patients with subacute limbic and brain-stem dysfunction and testicular cancer contains antibodies against a protein found in normal brain and in testicular tumors. Detection of these antibodies supports the paraneoplastic origin of the neurologic disorder and could be of diagnostic importance. (+info)
(7/970) Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits.
Febrile (fever-induced) seizures affect 3-5% of infants and young children. Despite the high incidence of febrile seizures, their contribution to the development of epilepsy later in life has remained controversial. Combining a new rat model of complex febrile seizures and patch clamp techniques, we determined that hyperthermia-induced seizures in the immature rat cause a selective presynaptic increase in inhibitory synaptic transmission in the hippocampus that lasts into adulthood. The long-lasting nature of these potent alterations in synaptic communication after febrile seizures does not support the prevalent view of the 'benign' nature of early-life febrile convulsions. (+info)
(8/970) Functional implications of the subunit composition of neuronal CaM kinase II.
The assembly of 6-12 subunits of Ca(2+)/calmodulin-dependent kinase II (CaM kinase II) into holoenzymes is an important structural feature of the enzyme and its postulated role as a molecular detector of Ca(2+) oscillations. Using single cell reverse transcriptase-polymerase chain reaction, we show that alpha- and beta-CaM kinase II mRNAs are simultaneously present in the majority of hippocampal neurons examined and that co-assembly of their protein products into heteromers is therefore possible. The subunit composition of CaM kinase II holoenzymes was analyzed by immunoprecipitation with subunit-specific monoclonal antibodies. Rat forebrain CaM kinase II consists of heteromers composed of alpha and beta subunits at a ratio of 2:1 and homomers composed of only alpha subunits. We examined the functional effect of the heteromeric assembly by analyzing the calmodulin dependence of autophosphorylation. Recombinant homomers of alpha- or beta-CaM kinase II, as well as of alternatively spliced beta isoforms, have distinct calmodulin dependences for autophosphorylation based on differences in their calmodulin affinities. Half-maximal autophosphorylation of alpha is achieved at 130 nM calmodulin, while that for beta occurs at 15 nM calmodulin. In CaM kinase II isolated from rat forebrain, however, the calmodulin dependence for autophosphorylation of the beta subunits is shifted toward that of alpha homomers. This suggests that Thr(287) in beta subunits is phosphorylated by alpha subunits present in the same holoenzyme. Once autophosphorylated, beta-CaM kinase II traps calmodulin by reducing the rate of calmodulin dissociation. (+info)