Mouse IHCs, the main sensory cells of the mammalian cochlea, were studied using whole-cell patch clamp techniques. Recordings were made from 453 IHCs (ranging from EI4.5-P20) positioned at the two extremes of the cochlea. Changes in the properties of K+ currents, spiking activity, and Ca2+ currents along with synaptic vesicle exocytosis, were investigated. IRCs begin to express voltage-gated K+ currents from as early as EI4.5. During the next few days the appearance of the Ca2 + current allows IHCs to fire broad spontaneous action potentials. The growth of these currents from just after birth speeds up each action potential and increases the spike frequency with basal cells spiking more frequently than apical cells. The disappearance of spiking activity, that occurs just before the onset of hearing (P12), changes IHCs into mature sound transducers. It is likely that spiking activity is important for the reorganization of neuronal connections during early development as previously suggested in other systems (Moody, 1998). In order for spiking activity to function as a developmental signal to the afferent fibres, neurotransmitter must be released from IHCs. Capacitance measurements (indicative of synaptic vesicle exocytosis i.e. neurotransmitter release) indicated that IHCs responded to an action potential with exocytosis from late embryonic stages. Immature cells contain at least two kinetically distinct vesicle pools that seem to become depleted following stimuli greater than 1.5 s. By contrast, exocytosis in mature cells is more graded, with no apparent depletion for the same stimulus duration, and shows a higher Ca2+ -efficiency. These changes may enable IHCs to relay accurate auditory information onto afferent fibres. Overall, the results suggest that IHC maturation goes through different stages in order to fulfill their role in cochlear development incorporating changes in their basolateral currents and synaptic machinery. The aim of this thesis was to examine developmental changes in the properties of spiking activity among apical and basal IHCs and investigate any differences that exist between the two regions. The ability of IHCs to respond to an action potential with exocytosis was studied at different developmental stages and the maturation of vesicle release properties was compared between the two extremes of the cochlea.

Thesis (doctoral)--University of Turku.

No description available.

The electrophysiological properties of dentate granule cells and hippocampal pyramidal neurons were examined with extracellular and intracellular recording techniques in the hippocampal slice. Intracellular analysis revealed that there may exist two populations of granule cells distinguishable by the presence or absence of non-linear current-voltage (I-V) membrane properties (anomalous rectification, AR). The granule cells exhibiting AR also maintained greater resting membrane potentials and action potential (AP) amplitude values. The membrane input resistance (Rn) and time constant (Tc) measurements were similar between the populations in response to hyperpolarizing current injection, but granule cells displaying AR had significantly higher Rn and Tc values in response to depolarizing pulses. Both groups also responded to maintained depolarizing current injection with repetitive AP discharges; however, this response accommodated. Upon termination of the depolarizing current injection, an afterhyperpolarization (AHP) resulted, the amplitude of which appeared to depend on the duration of the depolarizing pulse and not on the number of APs generated during the pulse. Stimulation of either the lateral (LPP) or medial (MPP) perforant paths evoked a monosynaptic EPSP followed by a depolarizing afterpotential (DAP) and a long afterhyperpolarization (LHP). In contrast, antidromic stimulation elicited a depolarizing-IPSP (D-IPSP) and a LHP. Both the DAP and D-IPSP were reversed by membrane depolarization, whereas, the LHP was inverted by membrane hyperpolarization. In all cases, however, the EPSP could not be inverted. Afterpotentials were associated with an increase in conductance, but the change accompanying the LHP was less than the DAP and D-IPSP. In addition, by reducing the [Ca]₀ and increasing the [Mg]₀, the DAP was attenuated and the LHP eliminated. Similar results were also obtained with the GABAB agonist, baclofen. Paired pulse stimulation of either the LPP or MPP resulted in the potentiation of the intracellular EPSP at condition-test (C-T) intervals less than 100 ms; however, simultaneous extracellular records from the granule cell layer (GCL) illustrated depression of the EPSP. The discrepancy between the extra- and intracellular recordings was shown to be related to the presence of the DAP. In addition, the MPP evoked test EPSP at C-T intervals greater than 150 ms exhibited inhibition regardless of whether it was recorded inside or outside the granule cell and this EPSP depression was partially due to the granule cell LHP. The LPP evoked test EPSP potentiated at all C-T intervals less than 1s when recorded from the outer molecular layer (OML) but was inhibited at both the GCL and intracellular recording sites. These data confirmed that postsynaptic processes contribute to the short-term alterations observed with paired pulse stimulation. The typical inhibition-potentiation-inhibition sequence of the perforant path (PP) evoked population spike (PS) was noted at C-T intervals of 20, 80 and 400 ms, respectively. The inhibition of the PS at 20 ms was abolished with perfusion of the GABA antagonist, bicuculline. In contrast, the PS inhibition at 400ms was unaffected by this treatment but was slightly attenuated by the gKca antagonist TEA. A number of factors appeared to contribute to the potentiation of the PS: 1) reduction in AP threshold; 2) the presence of the DAP; and 3) extrasynaptic events. In addition to the PS data from normal tissue, hippocampal slices from chronically kindled rats exhibited depression of the PS at all C-T intervals tested. This augmentation of inhibition was dependent on the presence of hippocampal afterdischarges but not on motor seizures. Perfusing the kindled slices with either bicuculline or lowered [Cl]₀ did not markedly reverse the enhanced inhibition at C-T intervals which displayed dramatic facilitation in normal slices. Intracellular recordings of granule cells obtained from kindled slices also exhibited an increase in the Rn and Tc. Both the alterations in inhibition and membrane characteristics appear to be localized to.the granule cells, since these changes were not observed in CA1 pyramidal neurons. These data indicate that short-term and long-term alterations in granule cell neuronal excitability are partially due to changes in the postsynaptic membrane. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 84-89).

国立情報学研究所で電子化したコンテンツを使用している。

Thesis (M.S.)--California Polytechnic State University, 2009. / Mode of access: Internet. Title from PDF title page; viewed on July 17, 2009. Major professor: Dr. Robert Szlavik. "Presented to the faculty of California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degrees [of] Master of Science in Engineering, with specialization in Biomedical Engineering, Bachelor's of Science in Electrical Engineering." "June 2009." Includes bibliographical references (p. 22).

Thesis (Ph.D.)--Biomedical Engineering, Georgia Institute of Technology, 2007. / Committee Chair: Potter, Steve; Committee Member: Butera, Robert; Committee Member: DeWeerth, Stephen; Committee Member: Schumacher, Eric; Committee Member: Wenner, Pete.

Thesis--Helsingfors University, 1938. / Includes bibliographical references (p. [71]-74).

Thesis (M.A.)--Ball State University, 2009. / Title from PDF t.p. (viewed on July 12, 2010). Research paper (M.A.), 3 hrs. Includes bibliographical references (p. 42-43).