Persistent effects of early augmented acoustic environment on the auditory brainstem.

Acoustic experiences significantly shape the functional organization of the auditory cortex during postnatal "critical periods." Here, we investigate the effects of a non-traumatic augmented acoustic environment (AAE) on the central nucleus of the inferior colliculus (ICC) and lower brainstem nuclei in rat during the critical period. Our results show that an AAE during P9-P28 had a persistent effect on the evoked auditory brainstem responses leading to a decreased latency and an increased amplitude of the response at and above the frequency of the stimulus used for the AAE. These findings are correlated with increased numbers of sites in the ICC that responded to the AAE frequency and show higher thresholds. There also were persistent effects in neurons with a best frequency higher than the AAE stimulus. These neurons showed decreased activity at low sound levels in the low frequency tail of the frequency response area. This was at, below and above the AAE stimulus frequency. Less often, increased activity at higher sound levels also was seen. Together, these findings suggest multifaceted interactions between activity-dependent plasticity, homeostasis, and development in the brainstem during the initial stages of hearing. A neonate exposed to an altered auditory environment may experience long-lasting change over the entire network of the auditory system.

[Functional and activity-dependent plasticity mechanisms in the adult and developing auditory brain]. / Mecanismos de plasticidad (funcional y dependiente de actividad) en el cerebro auditivo adulto y en desarrollo.

INTRODUCTION AND DEVELOPMENT: Sensory systems show a topographic representation of the sensory epithelium in the central nervous system. In the auditory system this representation originates tonotopic maps. For the last four decades these changes in tonotopic maps have been widely studied either after peripheral mechanical lesions or by exposing animals to an augmented acoustic environment. These sensory manipulations induce plastic reorganizations in the tonotopic map of the auditory cortex. By contrast, acoustic trauma does not seem to induce functional plasticity at subcortical nuclei. Mechanisms that generate these changes differ in their molecular basis and temporal course and we can distinguish two different mechanisms: those involving an active reorganization process, and those that show a simple reflection of the loss of peripheral afferences. Only the former involve a genuine process of plastic reorganization. Neuronal plasticity is critical for the normal development and function of the adult auditory system, as well as for the rehabilitation needed after the implantation of auditory prostheses. However, development of plasticity can also generate abnormal sensation-like tinnitus. Recently, a new concept in neurobiology so-called 'neuronal stability' has emerged and its implications and conceptual basis could help to improve the treatments of hearing loss. CONCLUSION: A combination of neuronal plasticity and stability is suggested as a powerful and promising future strategy in the design of new treatments of hearing loss.

Immunolocalization of vesicular glutamate transporters 1 and 2 in the rat inferior colliculus.

The inferior colliculus is a major relay nucleus in the ascending auditory pathways that receives multiple glutamatergic inputs. Vesicular glutamate transporters 1 and 2 (VGLUT1, VGLUT2) most often have complementary non-overlapping distributions and can be used to differentiate glutamatergic inputs. The present study therefore examined co-immunolabeling of VGLUT1 and VGLUT2 in three divisions of the rat inferior colliculus. Additional co-immunolabeling of microtubule-associated protein 2 and neuronal class III beta-tubulin provided visualization of neuronal soma and processes and allowed identification of axo-somatic versus axo-dendritic contacts. Results showed numerous VGLUT1 and 2 immunolabeled terminals in the central nucleus, lateral cortex and dorsal cortex. In all three divisions there was little to no co-containment of the two vesicular glutamate transporters indicating a complementary distribution. VGLUT1 made predominantly axo-dendritic connections in the neuropil, while VGLUT2 had many axo-somatic contacts in addition to axo-dendritic contacts. VGLUT2 immunolabeled terminals were numerous on the soma and proximal dendrites of many medium-to-large and large neurons in the central nucleus and medium to large neurons in the dorsal cortex. There were more VGLUT2 terminals than VGLUT1 in all divisions and more VGLUT2 terminals in dorsal and lateral cortices than in the central nucleus. This study shows that VGLUT1 and VGLUT2 differentiate complementary patterns of glutamatergic inputs into the central nucleus, lateral and dorsal cortex of the inferior colliculus with VGLUT1 endings predominantly on the dendrites and VGLUT2 on both dendrites and somas.

The cytoarchitecture of the inferior colliculus revisited: a common organization of the lateral cortex in rat and cat.

The inferior colliculus (IC) is the major component of the auditory midbrain and contains three major subdivisions: a central nucleus, a dorsal cortex, and a lateral cortex (LC). Discrepancies in the nomenclature and parcellation of the LC in the rat and cat seem to imply different, species-specific functions for this region. To establish a comparable parcellation of the LC for both rat and cat, we investigated its histochemistry and inputs. In both species, the deep lateral cortex is marked by a transition between the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) rich superficial cortex and a cytochrome oxidase (CO) rich central nucleus. In both species, focal injections of anterograde tracers in the cochlear nucleus at sites of known best frequency produced bands of labeled inputs in two different subdivisions of the IC. A medial band of axons terminated in the central nucleus, while shorter bands were located laterally and oriented nearly perpendicularly to the medial bands. In the rat, these lateral bands were located in the third, deepest layer of the lateral (external) cortex. In the cat, the bands were located in a region that was previously ascribed to the central nucleus, but now considered to belong to the third, deepest layer of the LC, the ventrolateral nucleus. In both species, the LC inputs had a tonotopic organization. In view of this parallel organization, we propose a common parcellation of the IC for rat and cat with a new nomenclature. The deep layer of the LC, previously referred to as layer 3 in the rat, is designated as the 'ventrolateral nucleus' of the LC, making it clear that this region is thought to be homologous with the ventrolateral nucleus in the cat. The similar organization of the LC implies that this subdivision of the IC has similar functions in cats and rats.

Pharmacological management for agitation and aggression in people with acquired brain injury.

BACKGROUND: Of the many psychiatric symptoms that may result from brain injury, agitation and/or aggression are often the most troublesome. It is therefore important to evaluate the efficacy of psychotropic medication used in its management. OBJECTIVES: To evaluate the effects of drugs for agitation and/or aggression following acquired brain injury (ABI). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and other electronic databases. We also searched the reference lists of included studies and recent reviews. In addition we handsearched the journals Brain Injury and the Journal of Head Trauma Rehabilitation. There were no language restrictions. The searches were last updated in June 2006. SELECTION CRITERIA: Randomised controlled trials (RCTs) that evaluated the efficacy of drugs acting on the central nervous system for agitation and/or aggression, secondary to ABI, in participants over 10 years of age. DATA COLLECTION AND ANALYSIS: We independently extracted data and assessed trial quality. Studies of patients within six months after brain injury and/or in a confusional state, were distinguished from those of patients more than six months post-injury, or who were not confused. MAIN RESULTS: Six RCTs were identified and included in this review. Four of theses evaluated the beta-blockers, propranolol and pindolol, one evaluated the central nervous system stimulant, methylphenidate and one evaluated amantadine, a drug normally used in parkinsonism and related disorders. The best evidence of effectiveness in the management of agitation and/or aggression following ABI was for beta-blockers. Two RCTs found propranolol to be effective (one study early and one late after injury). However, these studies used relatively small numbers, have not been replicated, used large doses, and did not use a global outcome measure or long-term follow-up. Comparing early agitation to late aggression, there was no evidence for a differential drug response. Firm evidence that carbamazepine or valproate is effective in the management of agitation and/or aggression following ABI is lacking. AUTHORS' CONCLUSIONS: Numerous drugs have been tried in the management of aggression in ABI but without firm evidence of their efficacy. It is therefore important to choose drugs with few side effects and to monitor their effect. Beta-blockers have the best evidence for efficacy and deserve more attention. The lack of evidence highlights the need for better evaluations of drugs for this important problem.

Granule cells in the cochlear nucleus sensitive to sound activation detected by Fos protein expression.

Granule cells are the smallest neuronal type in the cochlear nucleus (CN). Due to their small size, it is extremely difficult to record their sound-evoked activity with microelectrodes. Compared with large, non-granule cells, much less is known about their response properties to sound stimulation. Here, we use Fos, the nuclear regulatory protein, as a neuronal activity marker to determine the responsiveness of granule cells to sound in comparison to the larger neurons. The present study determined the threshold sensitivity and activation pattern of neurons in the three subdivisions of the CN with free-field sound stimulation in monaural, awake rats. Immunocytochemical localization of Fos was used as our metric for "sound activation." Neuronal types upregulating Fos expression in response to sound stimulation were further identified with Nissl counterstaining. Our results show that most CN cell types can upregulate Fos expression when sound activated and the number of Fos-expressing neurons is directly related to sound intensity. The threshold for Fos activation in granule cells is lower than that for non-granule cells. The number of Fos activated granule cells saturates at high sound intensity, while the number of Fos activated non-granule cells is a monotonic function. By comparing the patterns of sound-induced Fos expression in different CN cell types, it may be possible to predict features of sound-evoked activity in granule cells.

Laminar inputs from dorsal cochlear nucleus and ventral cochlear nucleus to the central nucleus of the inferior colliculus: two patterns of convergence.

The central nucleus of the inferior colliculus is a laminated structure composed of oriented dendrites and similarly oriented afferent fibers that provide a substrate for tonotopic organization. Although inputs from many sources converge in the inferior colliculus, how axons from these sources contribute to the laminar pattern has remained unclear. Here, we investigated the axons from the cochlear nuclei that terminate in the central nucleus of the cat and rat. After characterization of the best frequency of the neurons at the injection sites in the cochlear nucleus, the neurons were labeled with dextran in order to visualize their axons and synaptic boutons in the central nucleus. Quantitative methods were used to determine the size and distribution of the boutons within the laminar organization. Two components in the laminae were identified: (1) a narrow axonal lamina that included the largest fibers and largest boutons; (2) a wide axonal lamina, surrounding the narrow lamina, composed of thin fibers and only small boutons. The wide lamina was approximately 30-40% wider than the narrow lamina, and it often extended more than 100 microm beyond the larger boutons on each side. The presence of both thick and thin fibers within the acoustic striae following these injections suggests that large and small fibers/boutons within these bands may originate from different neuronal types in the dorsal and ventral cochlear nucleus. We conclude that the narrow laminae that contain large fibers and boutons originate from larger cell types in the cochlear nucleus. In contrast, the wide lamina composed exclusively of small boutons may represent an input from other, perhaps smaller neurons in the cochlear nucleus. Thus, two types of inferior colliculus laminar structures may originate from the cochlear nucleus, and the small boutons in the wide laminae may contribute a functionally distinct input to the neurons of the inferior colliculus.

Frequency-specific effects on cochlear responses during activation of the inferior colliculus in the Guinea pig.

The inferior colliculus (IC) is a major processing center in the ascending auditory pathway. The role of the IC in the descending efferent auditory system is less clear. Although the IC central nucleus (ICC) is the major relay station for the ascending auditory pathways, the IC's cortex receives its main input from the neocortex and nonauditory sources. The goal of this study was to determine if the IC subdivisions had different functions in the descending efferent auditory system. IC subdivisions were identified by their tuning curves evoked by tone stimulation, and the effects of localized electrical stimulation on the cochlear whole-nerve action potential (CAP). Sharp tuning curves were obtained from ICC in contrast to broad tuning curves from the lateral, external cortex. Electrical stimulation within the central nucleus had a sharply tuned effect on the CAP. The frequency region affected within the cochlea closely matched the best frequency of local cells within the central nucleus. The effect of electrical stimulation within the lateral, external cortex on the CAP was smaller in comparison to central nucleus stimulation. Similar to the broad tuning of cells within the lateral cortex, electrical stimulation had a broad frequency effect on CAP thresholds.

Head injury as a risk factor for Alzheimer's disease: the evidence 10 years on; a partial replication.

OBJECTIVE: To determine, using a systematic review of case-control studies, whether head injury is a significant risk factor for Alzheimer's disease. We sought to replicate the findings of the meta-analysis of Mortimer et al (1991). METHODS: A predefined inclusion criterion specified case-control studies eligible for inclusion. A comprehensive and systematic search of various electronic databases, up to August 2001, was undertaken. Two independent reviewers screened studies for eligibility. Fifteen case-control studies were identified that met the inclusion criteria, of which seven postdated the study of Mortimer et al. RESULTS: We partially replicated the results of Mortimer et al. The meta-analysis of the seven studies conducted since 1991 did not reach significance. However, analysis of all 15 case-control studies was significant (OR 1.58, 95% CI 1.21 to 2.06), indicating an excess history of head injury in those with Alzheimer's disease. The finding of Mortimer et al that head injury is a risk factor for Alzheimer's disease only in males was replicated. The excess risk of head injury in those with Alzheimer's disease is only found in males (males: OR 2.29, 95% CI 1.47 to 2.06; females: OR 0.91, 95% CI 0.56 to 1.47). CONCLUSIONS: This study provides support for an association between a history of previous head injury and the risk of developing Alzheimer's disease.

Pharmacological management for agitation and aggression in people with acquired brain injury.

BACKGROUND: Of the many psychiatric symptoms that may result from brain injury, agitation and/or aggression are often the most troublesome. It is therefore important to evaluate the efficacy of psychotropic medication used in its management. OBJECTIVES: To evaluate the effects of drugs for agitation and/or aggression following acquired brain injury (ABI). SEARCH STRATEGY: We searched MEDLINE (1966-2002), EMBASE (1980-2002) and the Cochrane Controlled Trials Register (1996-2002), Web of Science Citation Index, reference lists of papers meeting the inclusion criteria and recent reviews. We handsearched Brain Injury and the Journal of Head Trauma Rehabilitation. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) that evaluated the efficacy of drugs acting on the central nervous system for agitation and/or aggression, secondary to ABI, in participants over 10 years of age. Studies using lower levels of evidence (i.e. case series studies, single case studies and controlled group comparison studies), were collated in an appendix. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Authors were contacted where necessary for additional information. Studies of patients within six months after brain injury and/or in a confusional state, were distinguished from those of patients more than six months post-injury, or who were not confused. MAIN RESULTS: Six randomised controlled trials were identified. Four RCTs evaluated the beta-blockers, propranolol and pindolol, one RCT evaluated the central nervous system stimulant, methylphenidate and one RCT evaluated amantadine, a drug normally used in parkinsonism and related disorders. The best evidence of effectiveness in the management of agitation and/or aggression following ABI was for beta-blockers. Two RCTs found propranolol to be effective (one study early and one late after injury). However, these studies used relatively small numbers, have not been replicated, used large doses, and did not use a global outcome measure or long-term follow-up. Comparing early agitation to late aggression, there was no evidence for a differential drug response. Firm evidence that carbamazepine or valproate is effective in the management of agitation and/or aggression following ABI is lacking. REVIEWER'S CONCLUSIONS: Numerous drugs have been tried in the management of aggression in ABI but without firm evidence of their efficacy. It is therefore important to choose drugs with few side effects and to monitor their effect. Beta-blockers have the best evidence for efficacy and deserve more attention. The lack of evidence highlights the need for better evaluations of drugs for this important problem.

Expression of GABA(A) receptor subunits in the rat central nucleus of the inferior colliculus.

Expression of GABA(A) receptor (GABA(A)R) alpha(1), alpha(2), beta(2), gamma(1), gamma(2L) and gamma(2S) subunit mRNA was examined in three cell classes in the central nucleus of the rat inferior colliculus (CNIC). GABA(A)R alpha(1) and gamma(2L) subunit mRNA expression was greatest in large cells (over 25 microm long diameter), intermediate in medium sized cells (15 to 25 microm long diameter) and lowest in small cells (10 to 15 microm long diameter). GABA(A)R gamma(2S) and alpha(2) subunits had the opposite pattern, highest in the small cells, intermediate in medium cells and lowest in large cells. GABA(A)R beta(2) was significantly lower in small cells than the two other classes, while differences between large and medium cells were not significant. GABA(A)R gamma(1) subunit mRNAs expression was not above background in any of the three cell types assessed. The expression of GABA(A)R subunits suggests that cell classes in the rat CNIC may differ in their response to GABA and GABAergic drugs.

Distinct K currents result in physiologically distinct cell types in the inferior colliculus of the rat.

The inferior colliculus (IC) processes auditory information ascending from the brainstem. The response of the IC to this information and its ability to transform it is partly determined by the types of ionic currents that generate the intrinsic discharge patterns of IC neurons and their susceptibility to changes in the external environment. We have used whole-cell patch-clamp techniques on IC neurons in rat brain slices to characterize the potassium currents present and to correlate them with the firing patterns observed. Neurons in the IC can be classified into six physiologically distinct cell types. Each of these cell types has a firing pattern that is generated by a unique potassium current and set of cellular parameters. Sustained-regular cells show mainly delayed rectifier K(+) channels. Onset cells have a unique high-threshold tetraethylammonium-sensitive K(+) current. Pause-build cells have an A-current. Rebound-regular cells have calcium-dependent rebound depolarizations. Rebound-adapting cells have both an apamin-sensitive calcium-dependent K(+) current and a calcium-dependent rebound depolarization. Transient-rebound cells have a charybdotoxin-sensitive calcium-dependent K(+) current and a calcium-dependent rebound. Our data suggest that there would be similarities as well as differences among IC neurons in their responses to excitatory or inhibitory inputs. Furthermore, some cells are likely to show little or no plasticity and behave as simple relays of temporal and intensity information, whereas others are likely to transform their inputs.

Ascending efferent projections of the superior olivary complex.

The superior olivary complex conveys information about binaural time and intensity to higher centers in the auditory pathway. This information is sent primarily to the subdivisions of the inferior colliculus and to the nuclei of the lateral lemniscus. Olivary projections are the predominant afferents to the central nucleus of the inferior colliculus. Electron microscopic observations of axonal endings in the central nucleus suggest that the ipsilateral medial superior olive and contralateral lateral superior olive make excitatory synapses. In contrast, the axons from the ipsilateral lateral superior olive to the central nucleus contain glycine and have a morphology consistent with inhibitory synapses. Little is known about the transmitter types used by olivary projections to the nuclei of the lateral lemniscus, but they are presumed to be similar to the collicular projections. Olivary ascending efferents are tonotopically organized and terminate in laminae in the inferior colliculus. They combine with other laminar afferents and postsynaptic neurons to create fibro-dendritic laminae in the colliculus. The key to the functional organization of the olivary efferents is the possible segregation of excitatory olivary efferents from each other in "synaptic domains" located on the laminae. This segregation may be the major determinant of response properties in the colliculus. Olivary efferents may converge with other non-olivary afferents on the same postsynaptic neurons in the colliculus. Inhibitory efferents from the lateral superior olive are essential in shaping the response properties of neurons in the colliculus. Olivary efferents to the nuclei of the lateral lemniscus are also key components of ascending pathways that inhibit neurons in the midbrain.

Identification of cell types in brain slices of the inferior colliculus.

Different type neurons in the inferior colliculus may have different functions. Recent intracellular studies of the inferior colliculus suggest that intrinsic electrical properties contribute to discharge patterns, but the intrinsic discharge patterns have not been fully characterized in the central nucleus, the main part of the inferior colliculus. Whether different types of neurons are related to different discharge patterns is unclear. We have used intracellular and whole-cell patch clamp-recording techniques in a brain slice preparation to better characterize discharge patterns and cell types in the central nucleus. Several types of discharge pattern were found in the inferior colliculus in response to long pulses of intracellular depolarizations. Rebound and buildup-pauser discharges, together, comprise neurons with a sustained response and are the majority of the neurons in the inferior colliculus. Both of these types of discharge pattern could be adapting or regular. Onset discharges distinguished another group of neurons. Onset neurons can also entrain to higher frequency stimuli than sustained neurons. Discharge patterns are correlated with distinctive current-voltage relationships and with some aspects of dendritic morphology. However, the morphological data demonstrates that the discharge patterns do not correspond simply to disc-shaped (flat) or stellate (less-flat) categories. This is the first extensive analysis of electrophysiological properties of the central nucleus of the inferior colliculus in vitro. We suggest that there may be at least three functional classes of neurons and have implications for signal processing in the inferior colliculus.

Direct innervation of identified tectothalamic neurons in the inferior colliculus by axons from the cochlear nucleus.

The present study sought to identify tectothalamic neurons in the rat inferior colliculus that receive their innervation directly from the cochlear nuclei and to identify the axons that provide the innervation. A direct projection would bypass the binaural interactions of the superior olivary complex and provide the quickest route to the neocortex. Axons, primarily from the dorsal cochlear nucleus, were labeled with anterograde transport of dextran and terminated in the central nucleus of the inferior colliculus in a laminar pattern. Most labeled axons were thin and simply branched. Other axons were thicker, gnarly, less frequently observed and probably originated from the ventral cochlear nucleus. None had concentrated endbulbs or a nest of endings. Both types of axons terminated primarily in the central nucleus and layer 3 of the external cortex. This pattern suggests that the combination of these subdivisions in the rat are equivalent to the central nucleus as defined in other species. Tectothalamic neurons in the inferior colliculus in the same animals were identified by retrograde transport from the medial geniculate body and intracellular injection of Lucifer Yellow. A number of different cell types act as tectothalamic neurons and receive contacts from cochlear nucleus axons. These include flat cells (disc-shaped), less-flat cells and stellate cells. Two innervation patterns were seen: a combination of axosomatic and axodendritic contacts, and predominantly axodendritic contacts. Both patterns were seen in the central nucleus, but axosomatic contacts were seen less often in the other subdivisions. This is the first study to show direct connections between cochlear nuclear axons and identified tectothalamic neurons. The layers of axons from cochlear nuclei may provide convergent inputs to neurons in the inferior colliculus rather than the heavy inputs from single axons typical of lower auditory nuclei. Excitatory synapses made by axons from the cochlear nuclei on tectothalamic neurons may provide a substrate for rapid transmission of monaural information to the medial geniculate body.

Concurrent loss and proliferation of astrocytes following lateral fluid percussion brain injury in the adult rat.

Astrocyte populations were analyzed over a period of 1 month in the hippocampus following lateral fluid percussion (FP) brain injury. Rats (n = 23) were subjected either to a brain injury of moderate severity, or to anesthesia and surgery without injury (n = 7). At 3 days, 1, 2, or 4 weeks postinjury, subgroups of animals were sacrificed and the brains removed and sectioned for histochemical analysis. The density of astrocytes, identified with gold sublimate staining, decreased significantly in the ipsilateral hippocampus of injured rats 3 days following injury, eventually falling to 64% of the total astrocyte population present in uninjured animals by 1 week postinjury. One month postinjury, the density of hippocampal astrocytes had returned to 85% of the total number of astrocytes observed in the hippocampus of uninjured animals. In order to characterize the post-traumatic formation of new astrocytes, immunohistochemistry was performed using antibodies to proliferating cell nuclear antigen (PCNA) and to glial fibriallary acidic protein (GFAP). Positive immunolabeling for both PCNA and GFAP was most abundant at 3 days following FP brain injury in regions where the blood brain barrier was compromised, and was not detectable by 1 month postinjury. These results indicate that astrocyte proliferation after injury may be evoked by mitogens released from vascular sources, and may be an attempt to compensate for some of the astrocytic cell loss observed after injury.

Axons from anteroventral cochlear nucleus that terminate in medial superior olive of cat: observations related to delay lines.

The differences in path length of axons from the anteroventral cochlear nuclei (AVCN) to the medial superior olive (MSO) are thought to provide the anatomical substrate for the computation of interaural time differences (ITD). We made small injections of biotinylated dextran into the AVCN that produced intracellular-like filling of axons. This permitted three-dimensional reconstructions of individual axons and measurements of axonal length to individual terminals in MSO. Some axons that innervated the contralateral MSO had collaterals with lengths that were graded in the rostrocaudal direction with shorter collaterals innervating more rostral parts of MSO and longer collaterals innervating more caudal parts of MSO. These could innervate all or part of the length of the MSO. Other axons had restricted terminal fields comparable to the size of a single dendritic tree in the MSO. In the ipsilateral MSO, some axons had a reverse, but less steep, gradient in axonal length with greater axonal length associated with more rostral locations; others had restricted terminal fields. Thus, the computation of ITDs is based on gradients of axonal length in both the contralateral and ipsilateral MSO, and these gradients may account for a large part of the range of ITDs encoded by the MSO. Other factors may be involved in the computation of ITDs to compensate for differences between axons.

Intracellular recordings in response to monaural and binaural stimulation of neurons in the inferior colliculus of the cat.

The inferior colliculus (IC) is a major auditory structure that integrates synaptic inputs from ascending, descending, and intrinsic sources. Intracellular recording in situ allows direct examination of synaptic inputs to the IC in response to acoustic stimulation. Using this technique and monaural or binaural stimulation, responses in the IC that reflect input from a lower center can be distinguished from responses that reflect synaptic integration within the IC. Our results indicate that many IC neurons receive synaptic inputs from multiple sources. Few, if any, IC neurons acted as simple relay cells. Responses often displayed complex interactions between excitatory and inhibitory sources, such that different synaptic mechanisms could underlie similar response patterns. Thus, it may be an oversimplification to classify the responses of IC neurons as simply excitatory or inhibitory, as is done in many studies. In addition, inhibition and intrinsic membrane properties appeared to play key roles in creating de novo temporal response patterns in the IC.

Simultaneous anterograde labeling of axonal layers from lateral superior olive and dorsal cochlear nucleus in the inferior colliculus of cat.

The laminar organization of the central nucleus of inferior colliculus includes layers of axons that may be important in shaping the responses of neurons. Depending on their source, some layered axons are afferents that are superimposed and terminate on the same postsynaptic neurons, while other layered afferents, such as those from the ipsilateral and contralateral lateral superior olive, terminate side-by-side. The specific pattern of convergence may dictate which populations of axons are presynaptic to layered disc-shaped neurons in the central nucleus. We compared the distribution of afferent axons from the dorsal cochlear nucleus and the lateral superior olive to the contralateral inferior colliculus in the cat. Injection sites in cochlear nucleus and superior olive were physiologically characterized by extracellular recordings of single and multiple units in response to monaural and binaural acoustic stimulation. Two separate injections were made in each case, and both injection sites contained units with overlapping best frequencies. Biotinylated dextran, fluorescent dextran, 3H-leucine, and wheat germ agglutinin conjugated to horseradish peroxidase were used as anterograde tracers. The present results show that layered axons from the dorsal cochlear nucleus and lateral superior olive are superimposed in part of the contralateral central nucleus. Both projections were arranged in rostro-caudally oriented axonal layers that converged in the ventral part of the central nucleus. However, in the dorsal part of the central nucleus, the same layer of axons from the dorsal cochlear nucleus did not terminate with afferents from the lateral superior olive. Within the overlapping layers in the ventral central nucleus, the overlap of axons from the dorsal cochlear nucleus and the lateral superior olive was uniform except for small patches that were usually smaller than the dendritic fields of disc-shaped neurons. These data suggest that the layers may create specific functional zones in the central nucleus of the inferior colliculus. One zone may contain neurons with binaural responses that combine the properties of the inputs from the contralateral lateral superior olive and the dorsal cochlear nucleus. A second zone may contain inputs from the cochlear nucleus but lack those of the lateral superior olive.

A monosynaptic GABAergic input from the inferior colliculus to the medial geniculate body in rat.

The goal was to investigate possible monosynaptic GABAergic projections from the inferior colliculus (IC) to thalamocortical neurons of the medial geniculate body (MGB) in the rat. Although there is little evidence for such a projection in other sensory thalamic nuclei, a GABAergic, ascending auditory projection was reported recently in the cat. In the present study, immunohistochemical and tract-tracing methods were used to identify neurons in the IC that contain GABA and project to the MGB. GABA-positive projection neurons were most numerous in the central nucleus and less so in the dorsal and lateral cortex. They were rare in the lateral tegmental system and brachium of the IC. The dorsal nucleus of the lateral lemniscus also contained GABA-positive projection neurons. In brain slices, stimulation of the brachium produced monosynaptic inhibitory postsynaptic potentials in morphologically identified thalamocortical relay neurons. The inhibitory potentials cannot originate locally, because they persisted when ionotropic glutamatergic transmission was blocked. Typically, brachium stimulation elicited a GABAA-mediated inhibitory potential followed by an excitatory potential and a longer latency GABAB-mediated inhibitory potential. We conclude that the GABA-containing neurons of the IC make short-latency, monosynaptic inputs to the thalamocortical projection neurons in the MGB. Such inputs may distinguish the main auditory pathway from indirect or tegmental auditory pathways as well as from other sensory systems. Monosynaptic inhibitory inputs to the medial geniculate may be important for the regulation of firing patterns in thalamocortical neurons.