Lateral Neostriatum Research Articles

The lateral neostriatum is necessary for compensatory ingestive behaviour after intravascular dehydration in female rats

Aberrant striatal function results in an array of physiological symptoms, including impaired consummatory and regulatory behaviours, which can lead to weight loss and dehydration. It was hypothesised, therefore, that cell loss in the neostriatum may contribute to altered fluid intake by regulating physiological signals related to dehydration status. To test this theory, rats with lesions of the lateral neostriatum and sham controls underwent a series of physiological challenges, including the experimental induction of intracellular and intravascular dehydration. No baseline differences in prandial or non-prandial drinking were observed, nor were differences in locomotor activity evident between groups. Furthermore, intracellular dehydration increased water intake in lesion rats in a manner comparable to sham rats. Interestingly, a specific impairment was evident in lesion rats after subcutaneous injection of poly-ethylene glycol was used to induce intravascular dehydration, such that lesion rats failed to adapt their water intake to this physiological change. The results suggest that the striatal lesions resulted in regulatory dysfunction by impairing motivational control over compensatory ingestive behaviour after intravascular hydration, while the physiological signals related to dehydration remain intact. Loss of these cells in neurodegenerative disorders, such Huntington’s disease, may contribute to regulatory changes evident in the course of the disease.

Nicotinamide prevents the effect of perinatal asphyxia on dopamine release evaluated with in vivo microdialysis 3 months after birth

The present study shows that nicotinamide prevents the long-term effect of perinatal asphyxia on dopamine release monitored with in vivo microdialysis in the neostriatum of 3-month-old rats. Perinatal asphyxia was induced by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath for 16 or 20 min. Sibling, spontaneous, and caesarean-delivered pups were used as controls. Saline or nicotinamide (0.8 mmol/kg, i.p.) was administered to control and asphyxia-exposed animals 24, 48, and 72 h after birth. After weaning, the rats were randomly distributed in laboratory cages for animal care under standard ad libitum laboratory conditions. Approximately 3 months after birth, control and asphyxia-exposed animals were implanted with microdialysis probes into the lateral neostriatum for measuring extracellular monoamine and metabolite levels with HPLC-coupled to an electrochemical detection system under basal, D-amphetamine, and K(+)-depolarising conditions. There was an asphyxia-dependent decrease of extracellular dopamine levels, mainly observed during the periods when D-amphetamine (100 microM) or KCl (100 mM) was added into the perfusion medium. Compared to that observed in caesarean-delivered controls, the effect of D-amphetamine on dopamine levels was decreased by approximately 30 and 70% in animals exposed to 16 and 20 min of perinatal asphyxia, respectively. The effect of K(+)-depolarisation was decreased by 45 and 83% in animals exposed to the same periods of asphyxia, respectively. Both effects were prevented by nicotinamide, even if the treatment started 24 h after the insult. The present results support the idea of nicotinamide as an interesting molecule, useful for protecting against anoxia/ischemia occurring at neonatal stages. Nicotinamide can help to restore NADH/NAD+ depletion, but also to inhibit PARP-1 overactivation, a mechanism of action that has attracted attention, representing a novel target for neuroprotection following insults involving energy failure.

Neural mechanisms of sexual imprinting

AbstractSexual imprinting is an early learning process by which a young animal acquires information which will help in choosing a sexual partner. It consists of two separate phases, an acquisition phase where features of the social environment are learnt, and a stabilisation phase in which, guided by the previously acquired social information, a preference for a sexual partner is established and stabilised, such that it cannot be altered subsequently. The stabilisation process is short and can be controlled experimentally. This review summarises research on the neural events accompanying consolidation in those brain areas which have previously been identified as important for imprinting. It shows that the period during which consolidation can occur can be shifted only within a certain time window, and demonstrates the fast adjustment of spine densities within the imprinting areas after consolidation has started. It further suggests that long term potentiation (LTP) and long term depression (LTD)-like mechanisms may be involved in this learning process, and that the immediate early genes ZENK and c-fos are expressed within the relevant imprinting areas in the course of consolidation. Evidence is presented for a prominent role of the lateral neostriatum in the imprinting process, and also for the involvement of the hippocampus in this type of early learning.

Contact call-driven Zenk protein induction and habituation in telencephalic auditory pathways in the Budgerigar (Melopsittacus undulatus): implications for understanding vocal learning processes.

Expression of the immediate early gene protein Zenk (zif 268, egr-1, NGF1A, Krox24) was induced in forebrain auditory nuclei in a vocal learning parrot species, the budgerigar (Melopsittacus undulatus), when the subjects either listened to playbacks of an unfamiliar contact call or to a contact call with which they had been familiarized previously. Auditory nuclei included the Field L complex (L1, L2a, and L3), the neostriatum intermedium pars ventrolateralis (NIVL), the neostriatum adjacent to caudal nucleus basalis (peri-basalis or pBas), an area in the frontal lateral neostriatum (NFl), the supracentral nucleus of the lateral neostriatum (NLs), and the ventromedial hyperstriatum ventrale (HVvm). The latter three nuclei are main sources of auditory input to the vocal system. Two patterns of nuclear staining were induced by contact call stimulation-staining throughout cell nuclei, which was exhibited by at least some neurons in all areas examined except L2a and perinucleolar staining, which was the only kind of staining exhibited in field L2a. The different patterns of Zenk staining indicate that auditory stimulation may regulate the Zenk-dependent transcription of different subsets of genes in different auditory nuclei. The numbers of neurons expressing Zenk staining increased from seven- to 43-fold over control levels when the birds listened to a repeating unfamiliar call. Familiarization of the subjects with the call stimulus, through repeated playbacks, greatly reduced the induction of Zenk expression to the call when it was presented again after an intervening 24-h interval. To determine if neurons exhibiting contact call-driven Zenk expression project to the vocal control system, call stimulation was coupled with dextran amines pathway tracing. The results indicated that tracer injections in the vocal nucleus HVo (oval nucleus of the hyperstriatum ventrale), in fields lateral to HVo and in NLs labeled many Zenk-positive neurons in HVvm, NFl, and NLs. These results support the idea that, in these neurons, egr-1 couples auditory stimulation to the synthesis of proteins involved in either the storing of new perceptual engrams for vocal learning or the processing of novel and/or meaningful acoustic stimuli related to vocal learning or the context in which it occurs.

Integration of information from both eyes by single neurons of nucleus rotundus, ectostriatum and lateral neostriatum in the zebra finch ( Taeniopygia guttata castanotis Gould)

Although the optic nerve in birds crosses completely, visual information from the ipsilateral eye also reaches the ectostriatum, the telencephalic statibon of the tectofugal pathway, by recrossing fibers. These recrossing projections connect the contralateral tectum opticum with the ipsilateral nucleus rotundus, which in turn projects to the ectostriatum. The ectostriatum itself projects to the overlying lateral neostriatum, an area which serves an important role in sexual imprinting. This study shows that contralateral and ipsilateral information converges on single neurons within the nucleus rotundus, the ectostriatal region and the lateral neostriatum. In the three brain areas almost all isolated neurons exhibited responses to contralateral as well as bilateral visual stimuli. The number of neurons responding to ipsilateral stimuli increases from nucleus rotundus to the lateral neostriatum. We did not find any neurons driven exclusively by ipsilateral stimuli. The strength of ipsilateral responses is rather weak within the nucleus rotundus and ectostriatum, but shows a sharp increase in the lateral neostriatum. For most neurons of nucleus rotundus and ectostriatum, an additional ipsilateral stimulus did not significantly affect the response to a contralateral one. In contrast, a strong excitatory effect can be found in the neostriatum. The results are in agreement with previous evoked-potential studies and give new insights on the integration of ipsilateral and contralateral stimuli in zebra finch tectofugal visual pathway.

Projections of the oval nucleus of the hyperstriatum ventrale in the budgerigar: Relationships with the auditory system

The afferent and efferent projections of a vocal control nucleus, the oval nucleus of the hyperstriatum ventrale (HVo), were mapped out in a parrot, the budgerigar (Melopsittacus undulatus) to determine the relationships of this nucleus to the auditory system. In budgerigars, HVo is connected to both the anterior forebrain pathway as well as to nuclei forming the descending projection system to the brainstem (Durand et al. [1997] J. Comp. Neurol. 377:179–206). Previous studies (Brauth et al. [1997] Proc. N. Y. Acad. Sci. 807:368–385; Durand and Brauth [1998] Neurosci Abstr 24:78.9) indicate that HVo lesions disrupt vocal performance and that HVo neurons show long latency electrophysiologic auditory responses. HVo has also been shown to receive input from neurons in the immediately adjacent HV (Durand et al. [1997] J. Comp. Neurol. 377:179–206). Thus, the focus of the present study was to elucidate relationships between HVo, its immediately adjacent surround and telencephalic auditory nuclei. The results show that, although the lateral and medial portions of HVo are interconnected with one another, inputs to these areas and their surrounds are distinctively different. The most substantial auditory system inputs are derived from the frontal lateral neostriatum (NFl) and supracentral nucleus of the lateral neostriatum (NLs); these project primarily to the lateral HVo and lateral HVo surround. The medial HVo and surround receive only sparse or modest input from auditory nuclei, including the caudomedial neostriatum (NCM), neostriatum intermedium pars lateralis (NIL), Fields L1 and L3, and the neostriatum intermedium pars ventrolateralis (NIVL). Other sources of input to the HVo surround include the hyperstriatum accessorium (HA), the supralaminar area of the frontal neostriatum (NAs), the ventral anterior archistriatum (AAv), the medial archistriatum (Am) and the medial HV. Neurons in the HV immediately medial to HVo project to a shell region around the entire nucleus. Both the ventral paleostriatum (VP) and ventral part of the central nucleus of the lateral neostriatum (NLc) project to HVo but not to the surround. Previously described projections (Durand et al., 1997) from HVo to the NAom, NLc, and the magnicellular nucleus of the lobus parolfactorius (LPOm) were confirmed. J. Comp. Neurol. 432:481–511, 2001. © 2001 Wiley-Liss, Inc.

Projections of the oval nucleus of the hyperstriatum ventrale in the budgerigar: Relationships with the auditory system

The afferent and efferent projections of a vocal control nucleus, the oval nucleus of the hyperstriatum ventrale (HVo), were mapped out in a parrot, the budgerigar (Melopsittacus undulatus) to determine the relationships of this nucleus to the auditory system. In budgerigars, HVo is connected to both the anterior forebrain pathway as well as to nuclei forming the descending projection system to the brainstem (Durand et al. [1997] J. Comp. Neurol. 377:179-206). Previous studies (Brauth et al. [1997] Proc. N. Y. Acad. Sci. 807:368-385; Durand and Brauth [1998] Neurosci Abstr 24:78.9) indicate that HVo lesions disrupt vocal performance and that HVo neurons show long latency electrophysiologic auditory responses. HVo has also been shown to receive input from neurons in the immediately adjacent HV (Durand et al. [1997] J. Comp. Neurol. 377:179-206). Thus, the focus of the present study was to elucidate relationships between HVo, its immediately adjacent surround and telencephalic auditory nuclei. The results show that, although the lateral and medial portions of HVo are interconnected with one another, inputs to these areas and their surrounds are distinctively different. The most substantial auditory system inputs are derived from the frontal lateral neostriatum (NFl) and supracentral nucleus of the lateral neostriatum (NLs); these project primarily to the lateral HVo and lateral HVo surround. The medial HVo and surround receive only sparse or modest input from auditory nuclei, including the caudomedial neostriatum (NCM), neostriatum intermedium pars lateralis (NIL), Fields L1 and L3, and the neostriatum intermedium pars ventrolateralis (NIVL). Other sources of input to the HVo surround include the hyperstriatum accessorium (HA), the supralaminar area of the frontal neostriatum (NAs), the ventral anterior archistriatum (AAv), the medial archistriatum (Am) and the medial HV. Neurons in the HV immediately medial to HVo project to a shell region around the entire nucleus. Both the ventral paleostriatum (VP) and ventral part of the central nucleus of the lateral neostriatum (NLc) project to HVo but not to the surround. Previously described projections (Durand et al., 1997) from HVo to the NAom, NLc, and the magnicellular nucleus of the lobus parolfactorius (LPOm) were confirmed.

Lesions in the budgerigar vocal control nucleus NLc affect production, but not memory, of english words and natural vocalizations.

This study investigates the role of the psittacid (parrot) central nucleus of the lateral neostriatum (NLc) in the production of learned English and natural vocalizations. Anatomic data have led researchers to define NLc alternately as the parrot homologue (Paton et al. [1981] J Neurosci. 11:1279-1288) or analogue (Striedter [1994] J Comp Neurol. 343:35-56) of the songbird high vocal center. Although numerous functional and electrophysiological studies have identified the role of various songbird vocal control nuclei, few similar functional studies have been performed in parrots, particularly with respect to NLc. In this study, both novel behavioral techniques and precise neurochemical lesions have been used to investigate the role of NLc in the production of learned vocalizations. The results suggest that NLc is involved in the production of, but not memory for, learned English and natural vocalizations. Specifically, NLc lesions disrupted the amplitude of amplitude-modulated vocalizations, but did not affect the frequency of the dominant or carrier signal of these vocalizations. These data provide some of the first evidence for the functional role of a parrot vocal control nucleus.

Auditory responses in the vocal motor system of budgerigars.

Budgerigars (Melopsittacus undulatus) are small Australian parrots that can imitate novel sounds in adulthood and therefore serve as a convenient model system for the study of vocal learning in adult animals. Previous anatomical studies had indicated that known auditory regions in the telencephalon of budgerigars are connected, albeit indirectly and rather sparsely, to vocal motor nuclei. Physiological evidence for connections between the auditory and vocal motor systems in budgerigars had been lacking, however. Here, we show that neurons in a telencephalic vocal motor region, i.e., the central nucleus of the lateral neostriatum (NLc), are responsive to auditory stimuli in isoflurane-anesthetized budgerigars. These responses are highly variable from trial to trial and frequently have latencies in excess of 100 ms. Neurons in NLc generally respond better to a budgerigar's own contact call than to a white noise stimulus, but the response preferences of NLc neurons in budgerigars are generally weaker and more diverse than the response preferences of neurons in the high vocal center of songbirds, which is probably analogous to NLc. These data indicate that parrots and songbirds, which have evolved the ability to learn vocalizations independently of one another, have both evolved physiologically effective connections between their auditory and vocal motor systems. Interestingly, however, the anatomical pathways by which the auditory and vocal motor systems interact, and the physiological details of how they communicate, appear to be significantly different between the two taxa.

Distribution of tyrosine hydroxylase-containing neurons and fibers in the brain of the budgerigar (Melopsittacus undulatus): general patterns and labeling in vocal control nuclei.

The distribution of tyrosine hydroxylase (TH) was mapped out in cells and fibers of the budgerigar (Melopsittacus undulatus) brain. Special attention was given to vocal control and auditory nuclei because budgerigars are a psittacine species in which both males and females are capable of lifelong vocal learning (Farabaugh et al. [1994] J. Comp. Psychol 108:81-92). The results show that TH staining in the central nucleus of the anterior archistriatum (AAc) resembled that of surrounding archistriatal fields, except for portions of the ventral archistriatum, which exhibited substantially more TH+ fibers. Fewer fibers and fiber baskets are present in the central nucleus of the lateral neostriatum (NLc) than in surrounding fields. Both the oval nuclei of the ventral hyperstriatum (HVo) and anterior neostriatum (NAo) exhibit less fiber staining than surrounding fields whereas fiber staining in the medial NAo (NAom) and magnicellular nucleus of the parolfactory lobe (LPOm) resemble that of surrounding fields. Staining in primary telencephalic auditory nuclei was extremely low. The only sex difference observed was slightly increased TH staining in LPOm of females compared with surrounding fields on some tissue sections. These findings are in contrast to previous findings in zebra finch (Poephila guttata), a close ended vocal learning songbird in which TH staining in vocal nuclei increases during development and remains greater than surrounding fields throughout adulthood. The present results therefore support the view that catecholamines act to inhibit vocal plasticity in adult vocal learning species. Several unique features of TH-immunoreactive (ir) cell groups were observed in the brainstem including sparsely scattered TH-ir somata immediately adjacent to the third ventricle, within the tectum, basal forebrain, archistriatum, and caudal neostriatum, and in the hippocampus. These latter populations have not been described in other avian species and resemble features of the catecholamine system generally found in either reptiles or mammals.

P75 NGFR mediates death of cholinergic neurons during postnatal development of the neostriatum in mice

We have previously shown that p75 nerve growth factor receptor (p75 NGFR) mediates apoptosis of ∼25% of the cholinergic basal forebrain neurons in normal control mice between postnatal day 6 and 15, but only of cholinergic neurons that lacked the nerve growth factor receptor TrkA. Here, we investigated whether and when the cholinergic neurons of the neostriatum, which express TrkA and p75 NGFR during early postnatal times, undergo p75 NGFR-mediated death. The cholinergic neurons in the lateral neostriatal regions expressed choline acetyltransferase (ChAT) earlier (postnatal day 3–6) than those of the medial regions and TrkA appeared before ChAT in all regions. Between postnatal day 6 and 10, ∼40% of the ChAT-positive neurons in the most lateral regions disappeared in control mice but not in p75 NGFR-deficient mice. During this time, the neostriatum of control, but not p75 NGFR-deficient, mice contained many apoptotic cells. This suggests that, similar to the cholinergic neurons of the basal forebrain, the neostriatal cholinergic neurons of control mice die and that this process is mediated by p75 NGFR. However, the roles of p75 NGFR and TrkA appear to be more complicated in the neostriatum where relatively few neurons express p75 NGFR during the death phase (and predominantly in the lateral neostriatum where the neuronal loss is greatest), and TrkA-positive as well as TrkA-negative neurons may be lost.

Loss of dopamine terminals in the medial prefrontal cortex increased the ratio of DOPAC to DA in tissue of the nucleus accumbens shell: role of stress

We examined whether dopamine depletion in the medial prefrontal cortex of the rat differentially affects basal and evoked dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) content in the subareas of the neostriatum and nucleus accumbens. Loss of ≈80% of tissue dopamine content in the medial prefrontal cortex did not significantly alter basal tissue concentrations of dopamine or DOPAC or the DOPAC : dopamine ratio in either the nucleus accumbens core or shell or the medial or lateral neostriatum. However, tail pressure stress significantly increased the DOPAC : dopamine ratio in the nucleus accumbens shell of lesioned rats. Because dorsal and ventral areas of the medial prefrontal cortex preferentially innervate the core and shell, respectively, we sought to determine whether the selective effect of lesions on dopamine terminals in the shell of the nucleus accumbens are paralleled by greater dopamine loss in the ventral medial prefrontal cortex. 6-Hydroxydopamine decreased tissue concentrations of dopamine in both the dorsal (−74%) and ventral medial prefrontal cortex (−68%). In lesioned rats, few tyrosine hydroxylase-immunoreactive fibers remained in the dorsal medial prefrontal cortex whereas a dense innervation remained in the ventralmost area. The present data suggest that the influence of mesocortical dopamine neurons on the dopamine projection to the nucleus accumbens shell is expressed only under conditions of stress. Furthermore, lesion-induced alterations in dopamine neurons projecting to the nucleus accumbens shell are not due to a more extensive loss of dopamine terminals in the ventral than in the dorsal medial prefrontal cortex.

Distribution of choline acetyltransferase and acetylcholinesterase in vocal control nuclei of the budgerigar (Melopsittacus undulatus).

The present study used histochemical methods to map the distributions of choline acetyl transferase (ChAT) and acetylcholinesterase (AChE) in the vocal control nuclei of a psittacine, the budgerigar (Melopsittacus undulatus). The distributions of ChAT and AChE in budgerigars appeared similar to that in oscine songbirds despite evidence that these systems have evolved independently. The magnicellular nucleus of the lobus parolfactorius in budgerigars, like the area X in songbirds, contained many ChAT labeled somata, fibers, and varicosities and stained densely for AChE. In contrast, the robust nucleus of the archistriatum (RA) and the supralaminar area of the frontal neostriatum in budgerigars, like the RA and the magnicellular nucleus of the neostriatum (MAN) in songbirds, respectively, contained few or no ChAT labeled somata, fibers, and varicosities and stained lightly for AChE. The central nucleus of the lateral neostriatum in budgerigars, like the higher vocal center (HVC) in songbirds, contained no ChAT labeled somata, moderate densities of ChAT labeled fibers and varicosities, and moderate levels of AChE staining. Two nuclei, the oval nucleus of the hyperstriatum ventrale (HVo) and the oval nucleus of the anterior neostriatum (NAo), contained no ChAT labeled somata, dense ChAT labeled fibers and varicosities, and moderate to high levels of AChE staining. The HVo and the NAo have no counterparts in songbirds but may be important vocal control nuclei in the budgerigar. Cholinergic enzymes are also described in other regions which may be involved in budgerigar vocal behavior, including the basal forebrain, the torus semicircularis, and the hypoglossal nuclei (nXII).

Distribution of choline acetyltransferase and acetylcholinesterase in vocal control nuclei of the budgerigar (Melopsittacus undulatus)

The present study used histochemical methods to map the distributions of choline acetyl transferase (ChAT) and acetylcholinesterase (AChE) in the vocal control nuclei of a psittacine, the budgerigar (Melopsittacus undulatus). The distributions of ChAT and AChE in budgerigars appeared similar to that in oscine songbirds despite evidence that these systems have evolved independently. The magnicellular nucleus of the lobus parolfactorius in budgerigars, like the area X in songbirds, contained many ChAT labeled somata, fibers, and varicosities and stained densely for AChE. In contrast, the robust nucleus of the archistriatum (RA) and the supralaminar area of the frontal neostriatum in budgerigars, like the RA and the magnicellular nucleus of the neostriatum (MAN) in songbirds, respectively, contained few or no ChAT labeled somata, fibers, and varicosities and stained lightly for AChE. The central nucleus of the lateral neostriatum in budgerigars, like the higher vocal center (HVC) in songbirds, contained no ChAT labeled somata, moderate densities of ChAT labeled fibers and varicosities, and moderate levels of AChE staining. Two nuclei, the oval nucleus of the hyperstriatum ventrale (HVo) and the oval nucleus of the anterior neostriatum (NAo), contained no ChAT labeled somata, dense ChAT labeled fibers and varicosities, and moderate to high levels of AChE staining. The HVo and the NAo have no counterparts in songbirds but may be important vocal control nuclei in the budgerigar. Cholinergic enzymes are also described in other regions which may be involved in budgerigar vocal behavior, including the basal forebrain, the torus semicircularis, and the hypoglossal nuclei (nXII). © 1996 Wiley-Liss, Inc.

Organization of afferent and efferent projections of the nucleus basalis prosencephali in a passerine, Taeniopygia guttata.

The connections of nucleus basalis (NB) of the rostral forebrain of the zebra finch were investigated electrophysiologically and with anterograde and retrograde tracing methods to determine their functional organization, the sources of their pontine afferents, and the targets of their telencephalic efferents. The nucleus was found to be partitioned into three major components, a rostral lingual part that received a hypoglossal projection via a lateral subnucleus of the principal sensory trigeminal nucleus (PrV), a middle beak part that received a trigeminal projection via a medial subnucleus of PrV, and a caudal auditory part that received a short latency auditory projection via the intermediate nucleus of the lateral lemniscus. Beak NB also received a projection from a paralateral lemniscal nucleus, and the dorsocaudal part of auditory NB and the medially adjacent neostriatum also received a projection from a lateral subnucleus of the superior vestibular nucleus (VS). The efferent projections of each of the three major parts of NB were mainly to the adjacent neostriatum frontale (NF), which then provided projections to the lobus parolfactorius (exclusive of area X), the lateral archistriatum intermedium (Ail), and the lateral neostriatum caudale (NCl). Ail received a projection from NCl and provided terminal fields to the contralateral NCl and the NF. The major projections of Ail, however, descended bilaterally through the brainstem via the occipitomesencephalic tracts, with dense terminations in the medial spiriform nucleus and with extensive bilateral terminations throughout the lateral reticular formation of the pons and medulla. For the most part, jaw, tongue, and tracheosyringeal motor nuclei did not receive terminations. The results suggest that NB in zebra finch, like NB in pigeon and duck, is likely to be a major component of trigeminal sensorimotor circuitry involved in feeding and in other oral-manipulative behaviors. Results also show that the auditory component of NB is not directly linked to the vocal control system at telencephalic levels, but the possibility remains that the lingual, beak, and auditory parts of NB play a role in vocalization by multisynaptic influences on cranial nerve motor nuclei innervating various parts of the vocal tract.

Repeated scopolamine injections sensitize rats to pilocarpine-induced vacuous jaw movements and enhance striatal muscarinic receptor binding

This experiment was conducted to determine if repeated administration of the muscarinic antagonist scopolamine could increase pilocarpine-induced vacuous jaw movements and also enhance muscarinic receptor binding. Rats received daily injections of either scopolamine (0.5 mg/kg IP) or saline for 14 days. On day 15 rats received no injections of scopolamine, but did receive injections of pilocarpine (1.0, 2.0 or 4.0 mg/kg IP) or saline. After administration of pilocarpine or saline, all rats were observed for vacuous jaw movements and rearing behavior. The day after pilocarpine injections, rats were sacrificed and samples of tissue from the lateral neostriatum were removed to assess muscarinic receptor binding using 3H-QNB as the ligand. Analyses of the vacuous jaw movement data indicated that there was a significant dose-related increase in vacuous jaw movements induced by pilocarpine, and also that there was a significant enhancement of pilocarpine-induced vacuous jaw movements in rats pretreated with repeated scopolamine injections. There was not a significant scopolamine × pilocarpine interaction, suggesting that pretreatment with scopolamine produced an apparent parallel shift in the pilocarpine dose-response curve. Pilocarpine significantly suppressed rearing behavior, and scopolamine pretreatment significantly enhanced the suppression of rearing produced by pilocarpine. Analysis of the receptor binding data indicated that there was a significant increase in the number of muscarinic receptor sites ( B max) in rats that received repeated scopolamine injections as compared to saline-treated rats. These results demonstrate that repeated administration of scopolamine sensitizes rats to the induction of vacuous jaw movements produced by pilocarpine, and also indicate that vacuous jaw movements may be a useful behavioral procedure for assessing striatal muscarinic supersensitivity.

Protective actions of human recombinant basic fibroblast growth factor on MPTP-lesioned nigrostriatal dopamine neurons after intraventricular infusion.

Basic fibroblast growth factor (bFGF, FGF-2) is a trophic factor for neurons and astrocytes and has recently been demonstrated in the vast majority of dopamine (DA) neurons of the ventral midbrain of the rat. Potential neuroprotective actions of FGF-2 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model have also been reported. The actions of the FGF-2 have now been further analyzed in a combined morphological and behavioural analysis in the MPTP model of the adult black mouse, using a continuous human recombinant FGF-2 (hrFGF-2) intraventricular (i.v.t.) administration in a heparin-containing (10 IU heparin/ml) mock cerebrospinal fluid (CSF) solution. Tyrosine hydroxylase (TH) immunocytochemistry in combination with computer assisted microdensitometry demonstrated a counteraction of the MPTP-induced disappearance of neostriatal TH-immunoreactive (ir) nerve terminals following the FGF-2 treatment. Unbiased estimates of the total number of nigral TH ir neurons, using stereological methods involving the optical disector (Olympus), showed that the MPTP-induced reduction in the number of nigral TH ir nerve cell bodies counterstained with cresyl violet (CV; by 56%) was partially counteracted by the FGF-2 treatment (by 26%). The behavioral analysis demonstrated an almost full recovery of the MPTP-induced reduction of the locomotor activity after FGF-2 treatment. This action was maintained also 1 week after cessation of treatment. The hrFGF-2 produced an astroglial reaction as determined in the lateral neostriatum and in the substantia nigra (SN) far from the site of the infusion, indicating that the growth factor may have reached these regions by diffusion to activate the astroglia. Immunocytochemistry revealed FGF-2 immunoreactivity (IR) in the nuclei of the astroglia cell population in the dorsomedial striatum and the microdensitometric and morphometric evaluation demonstrated an increase in the number, but not in the intensity, of these profiles on the cannulated side, suggesting the possibility that hrFGF-2 stimulates FGF-2 synthesis in astroglial cells with low endogenous FGF-2 IR. These results indicate that hrFGF-2, directly and/or indirectly via astroglia, upon i.v.t. infusion exerts trophic effects on the nigrostriatal DA system and may increase survival of nigrostriatal DA nerve cells exposed to the MPTP neurotoxin

Quantitative Autoradiographic Demonstration of Changes in Binding to NMDA-sensitive [3H]Glutamate and [3H]MK801, but not [3H]AMPA Receptors in Chick Forebrain 30 min After Passive Avoidance Training.

Day-old domestic chicks (Gallus domesticus) were trained on a one-trial passive avoidance task in which the aversive stimulus was an unpleasant tasting substance, methyl anthranilate. Thirty minutes later, localization of N-methyl-d-aspartic acid (NMDA)-sensitive [3H]glutamate receptor binding sites, [3H]MK801 and [3H]AMPA binding sites in 17 regions of the forebrain of methylanthranilate-trained and control (water-trained) chicks was determined using quantitative receptor autoradiography. Significant differences in binding to both MK801- and NMDA-sensitive glutamate receptors, but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, were found in three regions of the forebrain of trained compared to control chicks; two of these regions have been implicated from previous lesion, biochemical and morphological studies as playing a key role in the process of memory formation and storage following passive avoidance training. For NMDA-sensitive [3H]glutamate receptors, significant elevations in binding were observed in two regions, the left intermediate and medial hyperstriatum ventrale (IMHV) (39%) and the lobus parolfactorius (LPO) (34%), at 30 min post-training, but a decrease (44%) occurred in binding to the lateral neostriatum. Significant increases in binding to MK801 receptors were observed in the left IMHV (19%) and right IMHV (13%), and left LPO (22%) at 30 min post-training, though there was a decrease in the right LPO (15%). These findings, coupled with those described in a previous paper from our group (Burchuladze and Rose, Eur. J. Neurosci., 4, 533 - 538, 1992), demonstrate that a glutamate receptor subtype is involved in learning and memory formation in the chick.

Potentiation of synaptic responses in slices from the chick forebrain.

Coronal slices, containing part of the medial hyperstriatum ventrale (MHV), were cut from the left forebrains of domestic chicks and maintained in vitro. Records were made of the field responses evoked in the MHV by local electrical stimuli provided at 0.1 Hz. Two 1 min periods of stimulation at 5 Hz, separated by 10 min, were used in attempts to induce a persistent increase in the size of the postsynaptic response to test stimulation at 0.1 Hz. This procedure produced a potentiation which usually lasted longer than 2 h. The probability of inducing this persistent potentiation of the response (PPR) is not distributed evenly over the whole anteroposterior length of the MHV but is higher in slices that also contain the septo-mesencephalic tract ventrally. These are the slices that contain the intermediate part of the medial hyperstriatum ventrale (IMHV); an area that is essential for early behavioural learning. At this level PPR is not confined to the IMHV. It can also be produced in the lateral neostriatum in response to similar local stimulation at 5 Hz. No PPR was observed in either the caudal ectostriatum, or the paleostriatum.

No mediolateral differences in striatal autoreceptor-mediated modulation of dopamine release: In vivo voltammetric data

Medial and lateral neostriatum differ qualitatively in their sources of dopamine (DA) innervation and in their behavioural functions. The present study sought to ascertain whether these differences were reflected in their response to DA autoreceptor drugs. Fast cyclic voltammetry was used to measure stimulated DA release at medial and lateral carbon fibre microelectrodes. Metoclopramide and (+)-3-PPP were used as autoreceptor antagonist and agonist respectively. No differences were observed in the level of DA release evoked by stimulation or in the agonist and antagonist responses at medial or lateral sites. We therefore conclude that differences between medial and lateral striatal DA function are not evident at the autoreceptor level.