The main source of excitation to the ventral cochlear nucleus (VCN) is from glutamatergic auditory nerve afferents, but the VCN is also innervated by two groups of cholinergic efferents from the ventral nucleus of the trapezoid body. One arises from collaterals of medial olivocochlear efferents, and the other arises from neurons that project solely to the VCN. This study examines the action of cholinergic inputs on stellate cells in the VCN. T stellate cells, which form one of the ascending auditory pathways to the inferior colliculus, and D stellate cells, which inhibit T stellate cells, are distinguished electrophysiologically. Whole-cell recordings from stellate cells in slices of the VCN of mice demonstrate that most T stellate cells are excited by cholinergic agonists through three types of receptors, whereas all D stellate cells tested were insensitive to cholinergic agonists. Nicotinic excitation in T stellate cells has two components. The faster component was blocked by alpha-bungarotoxin and methyllycaconitine, suggesting that receptors contained alpha7 subunits; the slower component was insensitive to both. Muscarinic receptors excite T stellate cells by blocking a voltage-insensitive, "leak" potassium conductance. Our results suggest that cholinergic efferent innervation enhances excitation by sounds of T stellate cells, opposing the inhibitory action of cholinergic innervation in the cochlea that is conveyed indirectly through the glutamatergic afferents. The inhibitory action of D stellate cells on their targets is probably not affected by cholinergic inputs. Excitation of T stellate cells by cholinergic efferents would be expected to enhance the encoding of spectral peaks in noise.

The dorsal cochlear nucleus integrates acoustic with multimodal sensory inputs from widespread areas of the brain. Multimodal inputs are brought to spiny dendrites of fusiform and cartwheel cells in the molecular layer by parallel fibers through synapses that are subject to long-term potentiation and long-term depression. Acoustic cues are brought to smooth dendrites of fusiform cells in the deep layer by auditory nerve fibers through synapses that do not show plasticity. Plasticity requires Ca 2؉ -induced Ca 2؉ release; its sensitivity to antagonists of N-methyl-D-aspartate and metabotropic glutamate receptors differs in fusiform and cartwheel cells.A uditory nerve fibers bring acoustic information to the cochlear nucleus and feed it into several parallel pathways that ascend through the brainstem. Pathways through the dorsal cochlear nucleus (DCN) are thought to detect spectral cues for localizing sounds monaurally (1). Those through the ventral cochlear nucleus (VCN) encode spectral and temporal characteristics that allow sounds to be localized in the horizontal plane, through binaural circuits, and recognized.The DCN resembles the cerebellum, cartwheel cells being homologues of cerebellar Purkinje cells (2). Fusiform cells project to the inferior colliculus. Granule cells in the vicinity of the cochlear nuclei are innervated by diverse regions of the brain, including the dorsal column nuclei (1), vestibular periphery (3), and auditory nuclei (4, 5). Their unmyelinated axons, parallel fibers, contact spiny dendrites of fusiform and cartwheel cells. Myelinated auditory nerve fibers contact smooth basal dendrites of fusiform cells. The DCN resembles the electrosensory lobes in fishes even more closely (6, 7).In cerebellar circuits, the gain of one of two converging systems of inputs varies as a function of activity. Long-term depression (LTD) at parallel fiber synapses in cerebellar Purkinje cells evoked by coincident excitation through parallel fiber and climbing fiber synapses plays a role in coordination and motor learning (8). Long-term potentiation (LTP) and LTD at parallel fiber synapses are evoked in electric fishes by convergent excitation by parallel fibers and sensory afferents to compensate for an animal's own signals in localizing external sources (9). We show that principal cells of the DCN combine multimodal inputs through parallel fibers whose strength is modulated by activity with invariant acoustic input through auditory nerve fibers. MethodsCoronal slices (200 m) containing the DCN were prepared from ICR mice (Harlan-Sprague-Dawley) between 18 and 20 days old with an oscillating tissue slicer (VT1000S, Leica Microsystems, Nussloch, Germany). Slices were held in a 300-l chamber that was superfused at 3-5 ml͞min with oxygenated saline at Ϸ33°C. Experiments were done in accordance with the protocols and guidelines of the Animal Care and Use Committee at the University of Wisconsin, Madison.Whole-cell patch-clamp recordings were generally made with 3-to 5-M⍀ pipettes filled with a K-gluconate-base...

Significance Sequences derived from ancient viruses have been shown to make up a substantial part of animal genomes. Bornaviruses, a genus of nonsegmented, negative-sense RNA virus, also have left their DNA copies in the genomes of a number of vertebrate lineages. Recent studies have demonstrated that some endogenous bornavirus-like elements (EBLs) may have acquired functions in their hosts as a result of exaptation. In this study, we show that protein encoded by an EBL in the genome of the thirteen-lined ground squirrel efficiently blocks infection and replication of extant bornavirus. To our knowledge, this is the first report showing that endogenous nonretroviral RNA virus elements may function in antiviral defense, providing a potential role for RNA virus endogenization in host evolution.

Bornaviruses are nonsegmented negative-strand RNA viruses that establish a persistent infection in the nucleus and occasionally integrate a DNA genome copy into the host chromosomal DNA. However, how these viruses achieve intranuclear infection remains unclear. We show that Borna disease virus (BDV), a mammalian bornavirus, closely associates with the cellular chromosome to ensure intranuclear infection. BDV generates viral factories within the nucleus using host chromatin as a scaffold. In addition, the viral ribonucleoprotein (RNP) interacts directly with the host chromosome throughout the cell cycle, using core histones as a docking platform. HMGB1, a host chromatin-remodeling DNA architectural protein, is required to stabilize RNP on chromosomes and for efficient BDV RNA transcription in the nucleus. During metaphase, the association of RNP with mitotic chromosomes allows the viral RNA to segregate into daughter cells and ensure persistent infection. Thus, bornaviruses likely evolved a chromosome-dependent life cycle to achieve stable intranuclear infection.