Cellular Mechanisms for Information Coding in Auditory Brain Stem Nuclei. Laurence Trussell Introduction2. Techniques 3. The synaptic potential 3.1 Excitatory transmission 3.1.1 Time course of the synaptic response 3.1.2 Synaptic activation of glutamate receptors 3.2 Inhibition 3.3 Presynaptic regulation of synaptic transmission 4. Intrinsic properties of neurons 4.1 Choppers 4.2 Primary-like (PL) responses and phase locking 4.3 The MNTB mirrors bushy cell activity 4.4 Octopus cells and detection of coherent activity 4.5 Other coincidence detection mechanisms 4.6 Fine tuning of response properties in fusiform cells 5. Summary Acknowledgements References Figure legendsCellular Mechanisms for Information Coding in Auditory Brain Stem Nuclei. Laurence Trussell Oregon Hearing Research Center and Vollum Institute, L-335A Oregon Health Sciences University 3181 SW Sam Jackson Park Rd Portland, OR 97201 Phone 503-494-3424 FAX 503-494-3403 Email [email protected] Chapter 3 in Integrative Functions in the Mammalian Auditory Pathway, edited by D. Oertel, R.R. Fay and A.N Popper. New York: Springer 2002, pp. 72-98. Introduction The brain stem auditory nuclei carry out a wide variety of transformations of the signals carried by the auditory nerve. Although basic frequency and intensity information is first encoded in the cochlea, brain stem circuitry must perform further neural definitions and refinements of these parameters, as well as integrate the cues necessary for the localization of sounds in space. Each of these aspects is associated not just with certain cell types, morphologies, and synaptic connections, but with cells having characteristic electrical response profiles. Such response properties are an outcome of the complement of ion channels that the cells possess and of the dynamic properties of the synapses through which cells communicate. The link between the properties of channels, of synapses, and the higher-order functions of circuits is not simply correlative. Rather, we are beginning to understand the function of cellular and membrane properties in terms of the relationship between a given sound stimulus and the responses of the auditory nerve and different brain stem neurons in vivo. The cell types of the cochlear nuclei and superior olivary complex are numerous, and the full spectrum of their responses and functions is not yet clear. However, some key cell types have been well described and serve as excellent illustrations of the basic electrical themes. Auditory nerve fibers respond to simple acoustic stimuli with two general response profiles (Fig. 1; see Ruggero 1992). For low-frequency stimuli, nerve fibers fire action potentials or spikes in a phase-locked manner, i.e., with a spike occurring most often with a certain phase relationship to the sound stimulus. For high-frequency stimuli, responses show an initial peak at the onset of the sound, and then a rapid decline in firing rate down to a steady-state level of random (not phase-locked) activity. These responses are documented using a poststimulus-time histogram (PSTH), in which the time of occurrence of spikes during repeated presentations of a stimulus is recorded (Fig. 1); such histograms illustrate at a glance the temporal relationship between the sound stimulus and the firing of the neuron. Recordings made from neurons in the auditory brain stem show characteristic levels of transformation of the primary afferent (auditory nerve) response pattern, and indeed these transformations are used in part to define the cell type. For example, postsynaptic neurons in the ventral cochlear nucleus (VCN) may respond almost identically to the activity patterns of the auditory nerve fibers; such responses are termed “primary-like” or PL (Pfeiffer 1966; Rhode 1986). Alternatively, neurons may show subtle or major deviations from this pattern. The goal of this chapter is explore how, at a membrane level, these firing patterns in postsynaptic cells might arise during synaptic activity. In the process, we will outline basic concepts in the physiology of ion channels and synapses as they relate to the function of auditory neurons. -1-2. Techniques The earliest studies of single neurons in the brain stem used extracellular recording techniques, which allowed investigators to associate a stereotyped pattern of firing of action potentials with a particular sound stimulus. This approach led to the definition of cell types by response profile, such as the PL, “chopper”, or “onset” cells (Fig. 1). Further definition was made by associating the recording with a particular subregion of the brain stem, using histological tracking methods. However, additional characterization of the properties of individual cells required the use of intracellular recording techniques, which permit both higher-level resolution of electrical activity and the injection of dye into the cells to reveal dendritic branching patterns, axonal projections, and synaptic distribution (Oertel 1983; Smith and Rhode 1987, 1989). Such studies, although very difficult, have provided critical information about the relation between PSTH patterns, cell types, and the membrane potential. Most recently, the patch-clamp technique has been applied to single-cell analysis because of the comparative ease with which recordings can be obtained and because of the ability to voltage-clamp neurons and monitor ionic currents (Hamill et al. 1981). Such recordings require the use of brain-slice preparations which allow one to change the composition of the extracellular solution and thus better define the ionic species giving rise to a particular current. With this information, the ionic selectivity and the pharmacological sensitivity of an ion channel can be accurately defined. Drugs identified in this way can then be used to determine the contribution of the channel to the firing properties of the neurons. Individual neurons may also be labeled using dyes in the patch pipettes to provide morphological identification of the neuron after the voltage- or current-clamp recordings are complete, as shown in Figure 2. A drawback of the patch-clamp technique is that it is difficult to apply in the in vivo setting, although some success has been reported (Covey et al. 1996). Further development of these and other in vivo recording techniques will be key to progress in the field. Several further refinements and issues deserve mention. Electrical