Faculty Bibliography

Spike-timing-dependent plasticity (STDP) has attracted considerable experimental and theoretical attention over the last decade. In the most basic formulation, STDP provides a fundamental unit - a spike pair - for quantifying the induction of long-term changes in synaptic strength. However, many factors, both pre- and postsynaptic, can affect synaptic transmission and integration, especially when multiple spikes are considered. Here we review the experimental evidence for multiple types of nonlinear temporal interactions in STDP, focusing on the contributions of individual spike pairs, overall spike rate, and precise spike timing for modification of cortical and hippocampal excitatory synapses. We discuss the underlying processes that determine the specific learning rules at different synapses, such as postsynaptic excitability and short-term depression. Finally, we describe the success of efforts toward building predictive, quantitative models of how complex and natural spike trains induce long-term synaptic modifications

While it has been appreciated for decades that synapse location in the dendritic tree has a powerful influence on signal processing in neurons, the role of dendritic synapse location on the induction of long-term synaptic plasticity has only recently been explored. Here, we review recent work revealing how learning rules for spike-timing-dependent plasticity (STDP) in cortical neurons vary with the spatial location of synaptic input. A common principle appears to be that proximal synapses show conventional STDP, whereas distal inputs undergo plasticity according to novel learning rules. One crucial factor determining location-dependent STDP is the backpropagating action potential, which tends to decrease in amplitude and increase in width as it propagates into the dendritic tree of cortical neurons. We discuss additional location-dependent mechanisms as well as the functional implications of heterogeneous learning rules at different dendritic locations for the organization of synaptic inputs

The endolymphatic hydrops seen in Menire's disease (MD) results from an inner ear fluid disequilibrium that has a suspected inherited component. Aquaporin-2 and aquaporin-4 (AQP2 and AQP4) water transport proteins may contribute to abnormal fluid homeostasis seen in MD. Our objective was to screen for sequence alterations in AQP2 and AQP4 genes in a northern European population with MD. Amplification for AQP2 (n = 18) and AQP4 (n = 30) was performed for patients with MD. Sequences were screened with denaturing high powered liquid chromatography (DHPLC) and confirmed with sequencing. Allele frequencies were compared with previously reported normal populations. We found that DHPLC failed to identify sequence alterations in any sample. Sequencing identified three intronic and one 3' untranslated region polymorphism in AQP2, and one polymorphism upstream from the start codon in AQP4. Two of the AQP2 intronic allele frequencies showed an A and C allele enrichment, respectively, compared with a reported mixed population (0.389 A vs. 0.00 A; 0.389 C vs. 0.00 C, p<0.001). The remaining polymorphism showed statistical difference from three non-Caucasian populations (0.611 A vs. 0.389 A, 0.375 A, and 0.280 A, p<0.05). The AQP4 allele frequency in the MD population was statistically different from a previously published Japanese population (0.800 G vs. 0.620 G, p = 0.0053) but not from a reported Caucasian population. We concluded that aquaporin polymorphisms may contribute to MD. Additional studies are needed to confirm these findings in well-defined population isolates and to determine if these polymorphisms lead to altered AQP protein function or levels

OBJECTIVE: The objective of this study was to assess whether training on speech processed with an eight-channel noise vocoder to simulate the output of a cochlear implant would produce transfer of auditory perceptual learning to the recognition of nonspeech environmental sounds, the identification of speaker gender, and the discrimination of talkers by voice. DESIGN: Twenty-four normal-hearing subjects were trained to transcribe meaningful English sentences processed with a noise vocoder simulation of a cochlear implant. An additional 24 subjects served as an untrained control group and transcribed the same sentences in their unprocessed form. All subjects completed pre- and post-test sessions in which they transcribed vocoded sentences to provide an assessment of training efficacy. Transfer of perceptual learning was assessed using a series of closed set, nonlinguistic tasks: subjects identified talker gender, discriminated the identity of pairs of talkers, and identified ecologically significant environmental sounds from a closed set of alternatives. RESULTS: Although both groups of subjects showed significant pre- to post-test improvements, subjects who transcribed vocoded sentences during training performed significantly better at post-test than those in the control group. Both groups performed equally well on gender identification and talker discrimination. Subjects who received explicit training on the vocoded sentences, however, performed significantly better on environmental sound identification than the untrained subjects. Moreover, across both groups, pre-test speech performance and, to a higher degree, post-test speech performance, were significantly correlated with environmental sound identification. For both groups, environmental sounds that were characterized as having more salient temporal information were identified more often than environmental sounds that were characterized as having more salient spectral information. CONCLUSIONS: Listeners trained to identify noise-vocoded sentences showed evidence of transfer of perceptual learning to the identification of environmental sounds. In addition, the correlation between environmental sound identification and sentence transcription indicates that subjects who were better able to use the degraded acoustic information to identify the environmental sounds were also better able to transcribe the linguistic content of novel sentences. Both trained and untrained groups performed equally well ( approximately 75% correct) on the gender-identification task, indicating that training did not have an effect on the ability to identify the gender of talkers. Although better than chance, performance on the talker discrimination task was poor overall ( approximately 55%), suggesting that either explicit training is required to discriminate talkers' voices reliably or that additional information (perhaps spectral in nature) not present in the vocoded speech is required to excel in such tasks. Taken together, the results suggest that although transfer of auditory perceptual learning with spectrally degraded speech does occur, explicit task-specific training may be necessary for tasks that cannot rely on temporal information alone

Studies of hand manipulation neurons in posterior parietal cortex of monkeys suggest that their spike trains represent objects by the hand postures needed for grasping or by the underlying patterns of muscle activation. To analyze the role of hand kinematics and object properties in a trained prehension task, we correlated the firing rates of neurons in anterior area 5 with hand behaviors as monkeys grasped and lifted knobs of different shapes and locations in the workspace. Trials were divided into four classes depending on the approach trajectory: forward, lateral, and local approaches, and regrasps. The task factors controlled by the animal-how and when he used the hand-appeared to play the principal roles in modulating firing rates of area 5 neurons. In all, 77% of neurons studied (58/75) showed significant effects of approach style on firing rates; 80% of the population responded at higher rates and for longer durations on forward or lateral approaches that included reaching, wrist rotation, and hand preshaping prior to contact, but only 13% distinguished the direction of reach. The higher firing rates in reach trials reflected not only the arm movements needed to direct the hand to the target before contact, but persisted through the contact, grasp, and lift stages. Moreover, the approach style exerted a stronger effect on firing rates than object features, such as shape and location, which were distinguished by half of the population. Forty-three percent of the neurons signaled both the object properties and the hand actions used to acquire them. However, the spread in firing rates evoked by each knob on reach and no-reach trials was greater than distinctions between different objects grasped with the same approach style. Our data provide clear evidence for synergies between reaching and grasping that may facilitate smooth, coordinated actions of the arm and hand

Cases of carcinoma metastatic to the nasal cavity are rare. We report the case of a 63-year-old woman with a metastasis to the nasal cavity from a primary tracheal adenoid cystic carcinoma (ACC). The nasal tumor was treated with surgical resection. No evidence of any local recurrence was observed at 4 years of follow-up. To the best of our knowledge, no case of a tracheal ACC metastatic to the nasal cavity has been previously reported in the literature. Although rare, metastatic disease to the nasal cavity should be considered in patients who have a known primary carcinoma elsewhere and who present with nasal symptoms.