Reciprocal interactions between intralaminar and lateral thalamic nuclei in rats

The effect of the nootropic drug piracetam (100 mg/kg) on kindled seizures, kindling-induced learning deficits, and histological alterations due to changes in central excitability was investigated in Wistar rats. The animals were kindled by repeated i.p. injections of an initially subconvulsive dose of pentylenetetrazol (PTZ). As a control, piracetam or physiological saline was given 60 minutes before PTZ. Twenty-four hours after completion of kindling the rats were tested in a shuttle-box paradigm. Seven days after the final kindling injection, the animals received a challenge dose of PTZ. Finally, the brains of the rats were processed for histological investigation. Pentylenetetrazol-kindled animals showed increasing seizure scores, and a learning deficit in the shuttle-box. Piracetam had no effect either on kindling development or on the reaction to a challenge dose of PTZ, but it protected the animals against the kindling-induced reduction of learning performance. The substance had no effect on learning performance in control animals. In distinct hippocampal structures, a neuronal cell loss was found in kindled rats. Interestingly, piracetam counteracted this damage efficaciously. The effects of piracetam are discussed in terms of its cytoprotective action. It is suggested that a coadministration of piracetam with clinically used antiepileptic drugs might be useful in antiepileptic therapy.     

Organisation of the reticular thalamic projection to the intralaminar and midline nuclei in rats

Risk detection and reduction methods for persons at high risk of ischemic stroke involve screening and identification of risk factors. Population-based health surveys affirm a persistent dilemma in the inability to reduce the frequency of ischemic stroke risk factors, such as hypertension, cigarette smoking, obesity, and physical inactivity levels. These alarming trends indicate that "mass approach" policies and programs need to be implemented or rethought to attain maximum levels of benefit in ischemic stroke risk reduction for the entire community.     

Lesions of the pontine parabrachial nuclei eliminate successive negative contrast effects in rats.

Rats shifted from a high to a low concentration of sucrose make fewer licks for the low concentration than rats that experience only the low concentration of sucrose. This phenomenon, referred to as successive negative contrast, is eliminated after bilateral electrolytic lesions of the amygdala. Because the amygdala receives direct projections from the gustatory zone of the parabrachial nuclei of the pons (PBN), this experiment was designed to examine this phenomenon in 43 male rats with electrophysiologically guided bilateral electrolytic lesions of the PBN. The results of this experiment showed that lesions of the PBN fully prevent contrast in rats shifted from the high to the low concentration of sucrose. Thus, an intact PBN is essential for the occurrence of successive negative contrast effects in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acetylcholine contents and muscarinic receptor levels in frontal cortex, corpus striatum, and hippocampus of reserpinized rats and mice

The acetylcholine (ACh) levels in rat and mouse frontal cortex increased 155% and 124%, respectively, 24 h after ip reserpine 3 mg.kg-1. Striatal ACh contents, however, were diminished by 47% in rats and 80% in mice. ACh contents elevated 50% and scopolamine (Scop) depleted the ACh by 47% in mouse striatum 12 h following reserpine. Receptor binding assay showed that 24 h after reserpine the Bmax of [3H]quinuclidinyl benzilate ([3H]QNB) binding to muscarinic receptors increased in frontal cortex (by 33% in rats, by 30% in mice) and decreased in striatum (31% in rats, 26% in mice). In mouse hippocampus the ACh contents, Bmax, and affinity of muscarinic receptors lowered 63%, 19%, and 26%, respectively. But these changes were not seen in rat hippocampus.     

Effects of lesions of thalamic intralaminar and midline nuclei and internal medullary lamina on spatial memory and object discrimination

Male Sprague-Dawley rats received either radiofrequency lesions of the lateral internal medullary lamina (IML) or ibotenic acid lesions of the lateral intralaminar nuclei (ILN) and midline nuclei (MLN) or sham treatment. Neither lesion group was impaired in the retention of 3 object pair discriminations acquired before surgery nor in the acquisition of a new object pair after surgery. Rats with ILN, but not IML, lesions were impaired in acquiring an initial and 5 subsequent hidden platform locations in a water maze task. These results suggest that damage to both ILN and MLN are needed to produce spatial learning deficits and that extensive damage to the IML or ILN has no detectable effects on retrograde or anterograde memory of object discriminations.     

Lesions of the dorsal hippocampus or parietal cortex differentially affect spatial information processing.

The present experiments used 2 versions of a modified Hebb-Williams maze to test the role of the dorsal hippocampus (dHip) and parietal cortex (PC) in processing allocentric and egocentric space during acquisition and retention. Bilateral lesions were made to either the dHip or PC before maze testing (acquisition) or after maze testing (retention). The results indicate that lesions of the dHip impair allocentric maze acquisition, whereas lesions of the PC impair egocentric maze acquisition. During retention, lesions of the PC produced a significant impairment on both maze versions, whereas lesions of the dHip produced short-lived, transient impairments on both maze versions. These results suggest that during acquisition, the hippocampus and PC process spatial information in parallel; however, long-term retention of spatial information requires the PC with the dHIP as necessary for retrieval and/or access but not necessarily storage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Flavor and the frontal cortex.

Rats were trained to discriminate an aqueous compound of an odor and taste (amyl acetate and NaCl) from the components of the compound before removal of one olfactory bulb and the contralateral ventrolateral frontal cortex. In postoperative tests, experimental rats performed much more poorly than nonlesioned controls or controls which had all lesions made in the same hemisphere. However, there were no significant differences among groups on tests for detection of amyl acetate and NaCl. These results provide evidence that integration of taste and smell in the production of flavor occurs in the ventrolateral frontal cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of orbital frontal cortex damage on the modulation of defensive responses by rats in playful and nonplayful social contexts.

In a series of 3 experiments on rats, 2 hypotheses were tested: (a) that damage to the orbital frontal cortex (OFC) would alter the socially relevant context for executing defensive responses but not their performance and (b) that damage done to the OFC in early infancy would produce more deficits in social behavior than similar damage occurring in adulthood. Bilateral or unilateral OFC damage in adult males did not impair their ability to defend themselves during play fighting and when protecting their food but did impair their ability to modify the pattern of defense in response to different partners. Rats that sustained bilateral damage at 3 days of age not only had deficits in partner-related modulation of defense but also exhibited hyperactivity in their play. The findings thus supported the proposed hypotheses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transection of direct anterior thalamic afferents from the hippocampus: Effects on activity and active avoidance in rats.

Demonstrated the importance of the direct hippocampo-anterior thalamic component of the postcommissural fornix in the control of general locomotion and active avoidance; 40 adult male Sprague-Dawley rats were Ss in 3 experiments. Transection of anterior thalamic afferents from the hippocampal formation (subicular cortex), at the point where they exit from the fornix posterior to the septum, enhanced bidirectional active avoidance acquisition and increased general activity. This transection may also interrupt fibers to or from other thalamic nuclei and the anterior septum. However, destruction of connections of the anterior septum with the hippocampus, habenula, and thalamus by transection in the coronal plane anterior to the descending fornix columns, without damage to the subiculothalamic fibers, increased general activity levels without affecting active avoidance behavior. The activity increase in this case resembled that seen after septal lesions rather than that seen after hippocampal lesions. Thus, destruction of a single fornix component contributing afferents to the anterior thalamic nuclei reproduces at least part of the hippocampal syndrome. This suggests that these fibers contribute significantly to the control of these behaviors and may mediate active avoidance changes resulting from hippocampal and fornix damage. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time-dependent changes in amphetamine self-administration following frontal cortex ablations in rats.

Conducted 2 experiments with a total of 28 operated, 25 sham-operated, and 21 normal female Sprague-Dawley albino rats. Ss were trained to intravenously self-administer dextroamphetamine (.01 mg/kg per reward infusion) during daily 1-hr testing sessions. Following removal of frontal cortex, rates of dextroamphetamine self-administration were higher at early (3-5 days) postoperative intervals but lower at later (2-4 wks) postoperative intervals. These and other results indicate that, as a function of time after surgery, frontal Ss were first hyposensitive and then became increasingly hypersensitive to the rewarding effect of dextroamphetamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aging and flexible remembering: Contributions of conceptual span, fluid intelligence, and frontal functioning.

Aging attenuates the capacity to adaptively and flexibly use episodic memory at different levels of specificity. Older and younger adults were tested on a picture recognition task that required them to make episodic memory decisions at an item-specific (verbatim) versus category-based (gist-based) level on randomly intermixed trials. Specificity modulation was assessed using a measure of the likelihood that participants retrieved verbatim information in order to reject test items that were categorically related to studied items under item-specific recognition instructions (recollection rejection). We found that this measure positively correlated with conceptual span (an index of short-term semantic memory) and with level of fluid intelligence in older and younger adults. However, when we simultaneously considered each of four possible contributors (age, conceptual span, fluid intelligence, and frontal function), the only significant predictor of recollection rejection was the composite fluid intelligence measure (assessed by the Culture Fair Intelligence Test [Cattell & Cattell, 1960] and the Wechsler Adult Intelligence Scale—Revised Block Design subtest [Wechsler, 1981]). These findings suggest that interventions that facilitate adaptive specificity modulation in episodic memory may enhance the flexibility of thinking, and vice versa, in both older and younger adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the midline thalamic nuclei impair classical conditioning under partial but not continuous reinforcement conditions

Protein Phosphatase-1 (PP-1) appears to be the key component of the insulin signalling pathway which is responsible for bridging the initial insulin-simulated phosphorylation cascade with the ultimate dephosphorylation of insulin sensitive substrates. Dephosphorylations catalyzed by PP-1 activate glycogen synthase (GS) and simultaneously inactivate phosphorylase a and phosphorylase kinase promoting glycogen synthesis. Our in vivo studies using L6 rat skeletal muscle cells and freshly isolated adipocytes indicate that insulin stimulates PP-1 by increasing the phosphorylation status of its regulatory subunit (PP-1G). PP-1 activation is accompanied by an inactivation of Protein Phosphatase-2A (PP-2A) activity. To gain insight into the upstream kinases that mediate insulin-stimulated PP-1G phosphorylation, we employed inhibitors of the ras/MAPK, PI3-kinase, and PKC signalling pathways. These inhibitor studies suggest that PP-1G phosphorylation is mediated via a complex, cell type specific mechanism involving PI3-kinase/PKC/PKB and/or the ras/MAP kinase/Rsk kinase cascade. cAMP agonists such as SpcAMP (via PKA) and TNF-alpha (recently identified as endogenous inhibitor of insulin action via ceramide) block insulin-stimulated PP-1G phosphorylation with a parallel decrease of PP-1 activity, presumably due to the dissociation of the PP-1 catalytic subunit from the regulatory G-subunit. It appears that any agent or condition which interferes with the insulin-induced phosphorylation and activation of PP-1, will decrease the magnitude of insulin's effect on downstream metabolic processes. Therefore, regulation of the PP-1G subunit by site-specific phosphorylation plays an important role in insulin signal transduction in target cells. Mechanistic and functional studies with cell lines expressing PP-1G subunit site-specific mutations will help clarify the exact role and regulation of PP-1G site-specific phosphorylations on PP-1 catalytic function.     

Long latency event-related potentials in rats: response of amygdala, nucleus accumbens, dorsal hippocampus and frontal cortex to changes in reward characteristics of conditioned stimuli

Recent evidence points to a role of cytokines like tumor necrosis factor-alpha (TNF) in the generation of hyperalgesia not only in inflammatory, but also in neuropathic pain. We used the model of chronic constrictive injury (CCI) of one sciatic nerve in the mouse to investigate which of the two known TNF receptors is involved in the process that leads to hyperalgesia after nerve injury. Neutralizing antibodies to TNF, to the TNF receptor 1 (TNFR1), and to the TNF receptor 2 (TNFR2) were administered by epineurial injection once daily to mice with CCI. Testing of the animals' hind paws with thermal and innocuous mechanical stimuli revealed a reduction in thermal hyperalgesia and mechanical allodynia in mice treated with neutralizing antibodies to TNF and to TNFR1. Neutralizing antibodies to TNFR2 had no effect. We conclude that TNFR1, but not TNFR2, is mediating thermal hyperalgesia and mechanical allodynia after nerve injury.     

Recovery of delayed alternation in rats after lesions in medial frontal cortex and septum.

Two experiments using contingently reinforced T-maze alternation with 48 male Long-Evans and hooded rats found that (a) normal Ss, after achieving high accuracy in alternation with brief (0 sec) intertrial intervals (ITIs), dropped to chance levels with longer ITIs (90 sec) but reacquired effective alternation with additional practice; (b) small lesions in mediodorsal pregenual cortex had no effect on postoperative retention of alternation at either short or long ITIs; (c) however, small lesions in posterodorsal septum temporarily disrupted alternation at brief ITIs, whereas at long ITIs Ss chose randomly and never recovered; and (d) large lesions in medial frontal cortex disrupted retention of alternation at brief ITIs of 10 sec but significant recovery did occur with additional experience. Implications regarding task difficulty and locus of lesion for recovery of function are discussed. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear conditioning to tone, but not to context, is attenuated by lesions of the insular cortex and posterior extension of the intralaminar complex in rats.

C. Shi and M. Davis (see record 1999-00012-009) recently reported that combined lesions of the posterior extension of the intralaminar complex (PINT) and caudal insular cortex (INS) block acquisition but not expression of fear-potentiated startle to discreet conditioned stimuli (CSs) and a footshock unconditioned stimulus (US) and proposed that PINT-INS projections to the amygdala constitute the essential US pathways involved in fear conditioning. The present study further tested this hypothesis by examining whether PINT-INS lesions block fear conditioning (as measured by freezing) to diffuse-context and discrete-tone CSs, and whether posttraining lesions with continued CS–US training result in extinction to the CSs. Posttraining lesions resulted in a selective attenuation of tone conditoning, but context conditioning was unaffected by pre-and posttraining lesions. These results do not support the view that the PINT-INS represent the essential US pathway in fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of the effects of serotonin in the hippocampus and the entorhinal cortex

Among the molecular, cellular, and systemic events that have been proposed to modulate the function of the hippocampus and the entorhinal cortex (EC), one of the most frequently cited possibilities is the activation of the serotonergic system. Neurons in the hippocampus and in the EC receive a strong serotonergic projection from the raphe nuclei and express serotonin (5-HT) receptors at high density. Here we review the various effects of 5-HT on intrinsic and synaptic properties of neurons in the hippocampus and the EC. Although similar membrane-potential changes following 5-HT application have been reported for neurons of the entorhinal cortex and the hippocampus, the effects of serotonin on synaptic transmission are contrary in both areas. Serotonin mainly depresses fast and slow inhibition of the principal output cells of the hippocampus, whereas it selectively suppresses the excitation in the entorhinal cortex. On the basis of these data, we discuss the possible role of serotonin under physiological and pathophysiological circumstances.     

Differential effects of amphetamine and food deprivation on self-stimulation of the lateral hypothalamus and medial frontal cortex.

Intracranial self-stimulation of the lateral hypothalamus in 5 male Sprague-Dawley rats was markedly increased by subcutaneous dextroamphetamine administration and by food deprivation. In contrast, similar self-stimulation response rates obtained in the same Ss from the medial frontal cortex were unaffected by food deprivation and only slightly increased by dextroamphetamine administration. Furthermore, a large difference between dextro- vs levoamphetamine on response rate was obtained for lateral hypothalamic but not for medial frontal cortex self-stimulation. Results are consistent with a noradrenergic self-stimulation system for the lateral hypothalamus. Medial frontal cortex self-stimulation, however, appears to be mediated by a neuroanatomical and neurochemical system different from that of the lateral hypothalamus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of the effects of frontal cortical and thalamic lesions on measures of olfactory learning and memory in the rat

Rats were trained on an olfactory continuous delayed nonmatching-to-sample (DNMTS) task and then given 1 of 4 treatments: sham surgery or radio-frequency lesion of the lateral internal medullary lamina of the thalamus or of the frontal cortex along the medial wall or dorsal to the rhinal sulcus. Thalamic lesions produced persistent deficits on the continuous DNMTS task, and both the cortical lesions resulted in transient impairments that disappeared with continued training. Manipulations of stimulus set size and the delay between trials affected continuous DNMTS performance but did not exacerbate group differences. All 3 lesion groups performed normally when next trained on a discrimination task with odorants and go-no-go procedures comparable to continuous DNMTS. These results indicate that lesions did not affect ability to perform go-no-go procedures, to discriminate among odorants, or to use reference memory to respond on the basis of a fixed stimulus-response rule.     

Loss of the thalamic nuclei for "head direction" impairs performance on spatial memory tasks in rats.

This study sought to characterize the effects of removing the nuclei of primary importance in relaying the thalamic head direction signal to the hippocampal formation (the anterior dorsal [AD] and lateral dorsal [LD] nuclei) on the performance of a variety of spatial and nonspatial tasks. The results indicate that combined excitotoxic lesions of the AD and LD nuclei produce marked deficits on a variety of spatial tasks. These tasks included T-maze alternation and the ability to locate a hidden platform set at a fixed distance and fixed direction from a beacon in a Morris water maze. Although object recognition appeared unaffected, marked impairments were found in the ability to detect when an object was placed in a novel position (object-in-place memory). (PsycINFO Database Record (c) 2010 APA, all rights reserved)