Cholinergic septal afferent terminals preferentially contact neuropeptide Y-containing interneurons compared to parvalbumin-containing interneurons in the rat dentate gyrus. (41/1058)

Septal cholinergic neurons may affect hippocampal memory encoding and retrieval by differentially targeting parvalbumin (PARV)-containing basket cells and neuropeptide Y (NPY) interneurons. Thus, the cellular associations of cholinergic efferents, identified by the low-affinity, p75 neurotrophin receptor (p75(NTR)), with interneurons containing either PARV or NPY in the hilus of the rat dentate gyrus were examined in single sections using dual labeling immunoelectron microscopy. Most profiles immunoreactive (IR) for PARV and NPY were perikaryal and dendritic and found within the infragranular and central hilar regions, respectively, whereas most profiles with p75(NTR)-labeling were unmyelinated axons and axon terminals. Although PARV-labeled profiles were more numerous, p75(NTR)-labeled axons and terminals contacted few PARV-IR profiles compared to NPY-labeled profiles (2% of 561 for PARV vs 12% of 433 for NPY). Moreover, structures targeted by p75(NTR)-IR axon terminals varied depending on the presence of PARV or NPY immunoreactivity. p75(NTR)-IR terminals primarily contacted PARV-IR dendrites (87%) compared to somata (13%); however, they contacted more NPY-IR somata (57%) than dendrites (43%). p75(NTR)-labeled terminals formed exclusively symmetric (inhibitory-type) synapses with PARV-IR somata and dendrites; however, they formed mostly symmetric but also asymmetric (excitatory-type) synapses with NPY-IR somata and dendrites. These results suggest that septal cholinergic efferents in the dentate gyrus: (1) preferentially innervate NPY-containing interneurons compared to PARV-containing basket cells; and (2) may provide a more powerful (i.e., somatic contacts), yet functionally diverse (i.e., asymmetric and symmetric synapses), modulation of NPY-containing interneurons. Moreover, they provide evidence that neurochemical subsets of hippocampal interneurons can be distinguished by afferent input.  (+info)

Dopamine terminals in the rat prefrontal cortex synapse on pyramidal cells that project to the nucleus accumbens. (42/1058)

Afferents to the prefrontal cortex (PFC) from dopamine neurons in the ventral tegmental area have been implicated in working memory processes and in the pathogenesis of schizophrenia. Previous anatomical investigations have demonstrated that dopamine terminals synapse on dendritic spines and shafts of pyramidal cells in the PFC. Moreover, neurochemical and physiological studies suggest that dopamine modulates the activity of PFC neurons that project to the nucleus accumbens. However, whether this modulation involves direct synaptic input to cortico-accumbens projection neurons has not been determined. To address this question, retrograde transport of an attenuated strain of pseudorabies virus (PRV) from the nucleus accumbens was combined with immunoperoxidase labeling of tyrosine hydroxylase (TH) to identify dopamine terminals in the PFC. At survival times <48 hr, extensive dendritic distribution of immunogold labeling for PRV was observed in cortico-accumbens neurons. However, evidence consistent with trans-synaptic passage of PRV within this timeframe was observed only rarely. When examined at the electron microscopic level, immunogold labeling for PRV was localized to neuronal somata, proximal and distal dendrites, and dendritic spines. Some of these dendritic processes received symmetric synaptic input from TH-immunoreactive terminals. These data represent the first demonstration of dopamine synaptic contacts onto an identified population of pyramidal cells in the PFC. The findings have important implications for understanding how dopamine modulates cortical outflow to limbic regions in normal brain and pathological states such as schizophrenia.  (+info)

Localization of triiodothyronine in nerve ending fractions of rat brain. (43/1058)

Radioactive triiodothyronine reaching the rat brain after intravenous administration is rapidly and selectively taken up in the nerve ending fraction. A concentration gradient of radioactivity from brain cytosol to synaptosomes is observed at 5 min, increases linearly over the first hour, and is maintained for at least 10 hr. Radioactivity in the synaptosomes is due to triiodothyronine (90%) plus a single unidentified metabolite (10%). Approximately 85% of the synaptosomal radioactivity is released by osmotic disruption of the particles. The process of selective uptake, concentration, and retention of triiodothyronine in nerve terminals of the rat brain may be related to the sympathomimetic and behavior-altering effects of the thyroid hormones.  (+info)

Presynaptic calcium channels and the depletion of synaptic cleft calcium ions. (44/1058)

The entry of calcium ions (Ca(2+)) through voltage-gated calcium channels is an essential step in the release of neurotransmitter at the presynaptic nerve terminal. Because the calcium channels are clustered at the release sites, the flux of Ca(2+) into the terminal inevitably removes the ion from the adjacent extracellular space, the synaptic cleft. We have used the large calyx-type synapse of the chick ciliary ganglion to test for synaptic cleft Ca(2+) depletion. The terminal was voltage clamped at a holding potential (V(H)) of -80 mV and a depolarizing pulse was applied to a range of potentials (-60 to +60 mV). The voltage pulse activated a sustained inward calcium current and was followed, on return of the membrane potential to V(H), by an inward calcium tail current. The amplitude of the tail current reflects both the number of open calcium channels at the end of the voltage pulse and the Ca(2+) electrochemical gradient. External barium was substituted for calcium as the charge-carrying ion because initial experiments demonstrated calcium-dependent inactivation of the presynaptic calcium channels. Tail current recruitment was compared in calyx nerve terminals that remained attached to the postsynaptic neuron and therefore retained a synaptic cleft, with terminals that had been fully isolated. In isolated terminals, the tail currents exhibited recruitment curves that could be fit by a Boltzmann distribution with a mean V(1/2) of 0.4 mV and a slope factor of 5.4. However, in attached calyces tail current recruitment was skewed to depolarized potentials with a mean V(1/2) of 11.9 mV and a slope factor of 12.0. The degree of skew of the recruitment curve in the attached calyces correlated with the amplitude of the inward current evoked by the step depolarization. The simplest interpretation of these findings is that during the depolarizing pulse Ba(2+) is removed from the synaptic cleft faster than it is replenished, thus reducing the tail current by reducing the driving force for ion entry. Ca(2+) depletion during presynaptic calcium channel activation is likely to be a general property of chemical transmission at fast synapses that sets a functional limit to the duration of sustained secretion. The synapse may have evolved to minimized cleft depletion by developing a calcium-efficient mechanism to gate transmitter release that requires the concurrent opening of only a few low conductance calcium channels.  (+info)

Non-quantal acetylcholine release is increased after nitric oxide synthase inhibition. (45/1058)

After anticholinesterase treatment, depolarization of the postsynaptic muscle membrane by about 5 mV develops due to non-quantally released acetylcholine from the motor nerve terminal and can be revealed as hyperpolarization by the addition of curare (H-effect). The H-effect increases significantly to 8.7 mV after inhibition of NO-synthase by L-nitroarginine methylester (L-NAME) whilst no changes in the amplitude and frequency of quantal miniature endplate potentials are observed.  (+info)

Ca(2+) influx inhibits dynamin and arrests synaptic vesicle endocytosis at the active zone. (46/1058)

Ca(2+) entry into nerve terminals through clusters of voltage-dependent Ca(2+) channels (VDCCs) at active zones creates a microdomain of elevated intracellular free Ca(2+) concentration ([Ca(2+)](i)) that stimulates exocytosis. We show that this VDCC-mediated [Ca(2+)](i) elevation has no specific role in stimulating endocytosis but can inhibit endocytosis evoked by three different methods in isolated mammalian nerve terminals. The inhibition can be relieved by using either VDCC antagonists or fast, but not slow, binding intracellular Ca(2+) chelators. The Ca(2+)-dependent inhibition of endocytosis is mimicked in vitro by a low-affinity inhibition of dynamin I vesiculation of phospholipids. Increased [Ca(2+)](i) also inhibits dynamin II GTPase activity and receptor-mediated endocytosis in non-neuronal cells. VDCC-meditated Ca(2+) entry inhibits dynamin-mediated endocytosis at the active zone and provides neurons with a mechanism to clear recycling vesicles to nonactive zone regions during periods of high activity.  (+info)

alpha-Melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression. (47/1058)

The hypothalamic arcuate nucleus has an essential role in mediating the homeostatic responses of the thyroid axis to fasting by altering the sensitivity of prothyrotropin-releasing hormone (pro-TRH) gene expression in the paraventricular nucleus (PVN) to feedback regulation by thyroid hormone. Because agouti-related protein (AGRP), a leptin-regulated, arcuate nucleus-derived peptide with alpha-MSH antagonist activity, is contained in axon terminals that terminate on TRH neurons in the PVN, we raised the possibility that alpha-MSH may also participate in the mechanism by which leptin influences pro-TRH gene expression. By double-labeling immunocytochemistry, alpha-MSH-IR axon varicosities were juxtaposed to approximately 70% of pro-TRH neurons in the anterior and periventricular parvocellular subdivisions of the PVN and to 34% of pro-TRH neurons in the medial parvocellular subdivision, establishing synaptic contacts both on the cell soma and dendrites. All pro-TRH neurons receiving contacts by alpha-MSH-containing fibers also were innervated by axons containing AGRP. The intracerebroventricular infusion of 300 ng of alpha-MSH every 6 hr for 3 d prevented fasting-induced suppression of pro-TRH in the PVN but had no effect on AGRP mRNA in the arcuate nucleus. alpha-MSH also increased circulating levels of free thyroxine (T4) 2.5-fold over the levels in fasted controls, but free T4 did not reach the levels in fed controls. These data suggest that alpha-MSH has an important role in the activation of pro-TRH gene expression in hypophysiotropic neurons via either a mono- and/or multisynaptic pathway to the PVN, but factors in addition to alpha-MSH also contribute to the mechanism by which leptin administration restores thyroid hormone levels to normal in fasted animals.  (+info)

Evaluation of the histamine H1-antagonist-induced place preference in rats. (48/1058)

The place preferences by some histamine H1 antagonists, such as tripelennamine, optical isomers of chlorpheniramine (dl-, d- and l-forms) and pyrilamine, in rats were evaluated with the conditioned place preference paradigm. In the present study, tripelennamine and all of the optical isomers of chlorpheniramine, but not pyrilamine, produced a significant place preference. The degree of the place preference induced by optical isomers of chlorpheniramine (6.0 mg/kg) did not correlate with the H1-antagonistic potency of these drugs, suggesting that H1-antagonist-induced place preferences are not mediated by H1-receptor blockade. The tripelennamine (3.0 mg/kg)- and dl-chlorpheniramine (6.0 mg/kg)-induced place preferences were completely abolished by pretreatment with the dopamine D1-receptor antagonist SCH23390 (0.05 mg/kg). Furthermore, the doses of H1 antagonists that induced a place preference significantly reduced the levels of DOPAC, which may be mediated by inhibition of dopamine uptake, in the limbic forebrain (including the nucleus accumbens and olfactory tubercle). These results suggest that some H1 antagonists induce rewarding effects, which may be mediated by the activation of dopamine D1 receptors, followed by the inhibition of dopamine uptake.  (+info)