Bassoon-disruption slows vesicle replenishment and induces homeostatic plasticity at a CNS synapse.

Endbulb of Held terminals of auditory nerve fibers (ANF) transmit auditory information at hundreds per second to bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN). Here, we studied the structure and function of endbulb synapses in mice that lack the presynaptic scaffold bassoon and exhibit reduced ANF input into the AVCN. Endbulb terminals and active zones were normal in number and vesicle complement. Postsynaptic densities, quantal size and vesicular release probability were increased while vesicle replenishment and the standing pool of readily releasable vesicles were reduced. These opposing effects canceled each other out for the first evoked EPSC, which showed unaltered amplitude. We propose that ANF activity deprivation drives homeostatic plasticity in the AVCN involving synaptic upscaling and increased intrinsic BC excitability. In vivo recordings from individual mutant BCs demonstrated a slightly improved response at sound onset compared to ANF, likely reflecting the combined effects of ANF convergence and homeostatic plasticity. Further, we conclude that bassoon promotes vesicular replenishment and, consequently, a large standing pool of readily releasable synaptic vesicles at the endbulb synapse.

[Architectonics of thalamic anterior dorsal and reticular nuclei of women's brain].

Architectonics of anterior dorsal and reticular nuclei of the thalamus was studied. A study set consisted of 5 specimens from the brain collection of the Research Neurological Center of the Russian Academy of Medical Sciences. Specimens were female, aged 19--59 years, all right-handed, who died suddenly and had no neurological, severe somatic or mental diseases during life. The following parameters were measured: neuron density, satellite glia density, density of satellite-surrounded neurons. The individual variability in neuron density was found. It was more pronounced in the reticular nucleus compared to the anterior dorsal nucleus. The variability of satellite glia density was higher in anterior dorsal nucleus; no differences in density of satellite-surrounded neurons were seen between nuclei studied. Between-hemisphere asymmetry with greater values on the left hemisphere was seen for the neuron and satellite glia densities in the anterior dorsal nucleus compared to the reticular nucleus. The density of satellite-surrounded neurons was greater in the anterior dorsal nucleus of the left hemisphere and in the reticular nucleus of the right hemisphere.

Synaptic organization of thalamocortical axon collaterals in the perigeniculate nucleus and dorsal lateral geniculate nucleus.

We examined the synaptic targets of large non-gamma-aminobutyric acid (GABA)-ergic profiles that contain round vesicles and dark mitochondria (RLD profiles) in the perigeniculate nucleus (PGN) and the dorsal lateral geniculate nucleus (dLGN). RLD profiles can provisionally be identified as the collaterals of thalamocortical axons, because their ultrastrucure is distinct from all other previously described dLGN inputs. We also found that RLD profiles are larger than cholinergic terminals and contain the type 2 vesicular glutamate transporter. RLD profiles are distributed throughout the PGN and are concentrated within the interlaminar zones (IZs) of the dLGN, regions distinguished by dense binding of Wisteria floribunda agglutinin (WFA). To determine the synaptic targets of thalamocortical axon collaterals, we examined RLD profiles in the PGN and dLGN in tissue stained for GABA. For the PGN, we found that all RLD profiles make synaptic contacts with GABAergic PGN somata, dendrites, and spines. In the dLGN, RLD profiles primarily synapse with GABAergic dendrites that contain vesicles (F2 profiles) and non-GABAergic dendrites in glomerular arrangements that include triads. Occasional synapses on GABAergic somata and proximal dendrites were also observed in the dLGN. These results suggest that correlated dLGN activity may be enhanced via direct synaptic contacts between thalamocortical cells, whereas noncorrelated activity (such as that occurring during binocular rivalry) could be suppressed via thalamocortical collateral input to PGN cells and dLGN interneurons.

Beyond spatial memory: the anterior thalamus and memory for the temporal order of a sequence of odor cues.

Influential recent proposals state that the anterior thalamic (AT) nuclei constitute key components of an "extended hippocampal system." This idea is, however, based on lesion studies that used spatial memory tasks and there has been no evidence that AT lesions cause deficits in any hippocampal-dependent nonspatial tasks. The present study investigated the role of the AT nuclei in nonspatial memory for a sequence of events based on the temporal order of a list of odors, because this task has recently been shown to depend on the integrity of the hippocampal formation. After preoperative training, rats with excitotoxic lesions of the AT nuclei showed a severe and selective postoperative impairment when required to remember the order of pseudorandom sequences of six odors. The rats with AT lesions were able instead to learn two new tasks that required recognition memory and the identification of the prior occurrence of events independent of their order. These results strongly matched those described after hippocampal lesions and provide the first unequivocal evidence of a detrimental effect of an AT lesion on a nonspatial hippocampal-dependent memory task.

Differential immunolocalization of m2 and m3 muscarinic receptors in the anteroventral and anterodorsal thalamic nuclei of the rat.

In this study, to identify the precise localization of m2 and m3 muscarinic receptors in the anteroventral and anterodorsal thalamic nuclei of the rat, we used receptor-subtype-specific antibodies and characterized their immunolocalization patterns by light and electron microscopy. Many m2-positive neurons were distributed throughout these nuclei. Ultrastructural analysis showed that more than 30% of m2-positive dendritic profiles in these nuclei are proximal dendritic shafts. Moreover, a few m2-positive fiber terminals were found only in the anterodorsal thalamic nucleus. These m2-positive terminals were large (1.10+/-0.30 microm in diameter) and formed asymmetrical synapses with dendritic profiles. The m3-positive neurons were also distributed in both nuclei, and the m3-positive neuropil exhibited a significant staining gradient, with the most intense staining in the ventrolateral part of the anteroventral thalamic nucleus. This region receives the densest cholinergic input originating from the dorsal tegmental region. At the ultrastructural level, the majority of m3-positive dendritic profiles were more distal regions of the dendrites compared to the m2 receptors in the anteroventral thalamic nucleus. However, no significant difference in the intradendritic distribution pattern between m2 and m3 receptors was found in the anterodorsal thalamic nucleus, which receives no cholinergic input. These findings show the differential localization of m2 and m3 receptors in the anteroventral and anterodorsal thalamic nuclei, and suggest that the m3 receptors are spatially more closely associated with ascending cholinergic afferent fibers in the anteroventral thalamic nucleus.

Reduced number of mediodorsal and anterior thalamic neurons in schizophrenia.

BACKGROUND: The thalamus is a brain region of interest in the study of schizophrenia because it provides critical input to brain regions such as the prefrontal, cingulate, and temporal cortices, where abnormalities have been repeatedly observed in patients with schizophrenia. Postmortem anatomic studies have rarely investigated the thalamus in this population. METHODS: Postmortem tissue was obtained from the left hemisphere of eight male schizophrenic patients and eight male age-matched control subjects. The optical dissector stereologic procedure was used to count neurons in the mediodorsal (MD) and anteroventral/anteromedial (AV/AM) nuclei of the thalamus. RESULTS: The number of neurons and volume of the MD were significantly reduced by 35% and 24%, respectively. The MD cell number reduction was a consistent finding; every control subject had more and every schizophrenic subject had fewer than 3.5 million neurons. Neuron number was also significantly reduced (16%) in the AV/AM nuclei. CONCLUSIONS: The present data indicate that schizophrenia is associated with robust reductions in nerve cell numbers in nuclei that communicate with the prefrontal cortex and limbic system. These thalamic anatomic deficits may be responsible, in part, for previous reports of such prefrontal cortical abnormalities as reduced synaptic density, reduced volume, and metabolic hypofunction.