Paul B. Manis

Polarity of Long-Term Synaptic Gain Change Is Related to Postsynaptic Spike Firing at a Cerebellar Inhibitory Synapse

Long-term potentiation and depression (LTP and LTD) in excitatory synapses can coexist, the former being triggered by stimuli that produce strong postsynaptic excitation and the latter by stimuli that produce weaker postsynaptic excitation. It has not been determined whether these properties also apply to LTP and LTD in the inhibitory synapses between Purkinje neurons and the neurons of the deep cerebellar nuclei (DCN), a site that has been implicated in certain types of motor learning. DCN cells exhibit a prominent rebound depolarization (RD) and associated spike burst upon release from hyperpolarization. In these cells, LTP can be elicited by short, high-frequency trains of inhibitory postsynaptic potentials (IPSPs), which reliably evoke an RD. LTD is induced if the same protocol is applied with conditions where the amount of postsynaptic excitation is reduced. The polarity of the change in synaptic strength is correlated with the amount of RD-evoked spike firing during the induction protocol. Thus, some important computational principles that govern the induction of use-dependent change in excitatory synaptic efficacy also apply to inhibitory synapses.

Effects of deafferentation on the electrophysiology of ventral cochlear nucleus neurons

When cochlear pathology impairs the afferent innervation of the ventral cochlear nucleus (VCN), electrical responses of the auditory brainstem are altered and changes in cell and synaptic morphology are observed. However, the impact of deafferentation on the electrical properties of cells in the VCN is unknown. We examined the electrical properties of single neurons in the anterior and posterior VCN following bilateral cochlear removal in young rats. In control animals, two populations of cells were distinguished: those with a linear subthreshold current-voltage relationship and repetitive firing of action potentials with regular interspike intervals (type I), and those with rectifying subthreshold current-voltage relationships and phasic firing of 1-3 action potentials (type II). Measures of action potential shape further distinguished these two groups. Two weeks following cochlear removal, both electrical response patterns were still seen. Type I cells showed a higher input resistance. Deafferented single-spiking type II cells were slightly more depolarized, had smaller action potentials, smaller afterhyperpolarizations and shorter membrane time constants, whereas multiple-spiking type II cells were apparently unaffected. These changes in the electrical properties of VCN neurons following cochlear injury may adversely affect central processing of sounds presented acoustically or electrically by prostheses.

The parameter identification problem for the somatic shunt model

The somatic shunt model, a generalized version of the Rall equivalent cylinder model, is used commonly to describe the passive electrotonic properties of neurons. Procedures for determining the parameters of the somatic shunt model that best describe a given neuron typically rely on the response of the cell to a small step of hyperpolarizing current injected by an intrasomatic recording electrode. In this study it is shown that the problem of estimating model parameters for the somatic shunt model using physiological data is ill-posed, in that very small errors in measured data can lead to large and unpredictable errors in parameter estimates. If the somatic shunt is assumed to be a real property of the intact neuron, the effects of these errors are not severe when predicting EPSP waveshapes resulting from synaptic input at a given location. However, if the somatic shunt is assumed to be a consequence of a leakage pathway around the recording electrode, and a correction for the shunt is applied, then the instability of the inverse problem can introduce large errors in estimates of EPSP waveshape as a function of synaptic location in the intact cell. Morphological constraints can be used to improve the accuracy of the inversion procedure in terms of both parameter estimates and predicted EPSP responses.

Physiology of the Dorsal Cochlear Nucleus Molecular Layer

The dorsal cochlear nucleus (DCN) is a complex but elegantly organized division of the cochlear nucleus. Lorente de No (’81) recognized that the cortex of the nucleus (layers 1 and 2) bore a remarkable resemblance to the cerebellum, in both the structural characteristics of the cells and their organization. The chief organization of the nucleus is based on a concentric laminar arrangement of cells, their dendrites, and fiber systems, somewhat like a single cerebellar folium. A local cartesian framework can be imposed on the nucleus, where the principal axes are depth (perpendicular to the local surface), the striai axis (parallel to the long axis of the nucleus and to the unmyelinated parallel fibers in the molecular layer), and the transstriai axis (parallel to the isofrequency planes formed by the auditory nerve fibers). Subsequent anatomical studies have exposed further similarities between the outer layers of the DCN and the cerebellum. Although the two structures serve different functions, the common ontogenetic origins and parallel expression of proteins in corresponding cell types (Mugnaini and Morgan,’ 87; Mugnaini et al.,’ 87; Berrebi and Mugnaini, this volume; Berrebi et al.,’ 90) suggests that the two structures share some mechanisms of information processing.

Properties of cochlear nucleus neurons in primary culture

Dissociated primary cell cultures were derived from the cochlear nuclei (CN) of postnatal rats using standard techniques. Cultured cells differentiated morphologically, but their dendritic profiles were generally less specialized than those of CN cells in vivo. Physiologically, cultured cells could be divided into three classes: tonic, phasic and non-spiking cells, which differed in many of their fundamental biophysical properties. The percentage of cultured cells that spiked repetitively increased over time to a maximum of 85% at 6 days. However, the percentage of cells that produced action potentials decreased with time in culture, from 91% during the first 8 days to less than 40% after 9 days. CN cells were successfully cultured in both serum-supplemented and serum-free (Neurobasal) media. More neurons survived at low plating densities in Neurobasal than in medium containing serum, although neuronal survival was similar at higher densities. Few neurons raised in the serum-free medium were spontaneously active; other response properties were similar to those of cells grown in the presence of serum. Although differentiation of CN cells in culture did not completely mirror the in vivo developmental pattern, these experiments demonstrate that primary culture represents a viable method for the in vitro study of CN neurons.

Protein kinase C mediates potentiation of synaptic transmission by phorbol ester at parallel fibers in the dorsal cochlear nucleus.

Many cells in the outer two layers of the dorsal cochlear nucleus (DCN) express high levels of the phospholipid-activated, calcium dependent kinase, protein kinase C (PKC), an enzyme that can phosphorylate numerous proteins involved in neurotransmission and postsynaptic signaling. We investigated the effects of stimulating PKC with phorbol esters (phorbol 12-13 diacetate; PDAc) on parallel fiber synaptic transmission in brain slices of the guinea pig DCN. Phorbol esters increased the amplitude of the postsynaptic components of the field potential, including the excitatory post-synaptic field potential (fEPSP) and the population spike following electric stimulation of parallel fibers. Phorbol esters simultaneously decreased paired-pulse facilitation, suggesting that transmitter release mechanisms were affected. Potentiation of synaptic transmission and diminished paired-pulse potentiation were also observed in intracellular recordings of DCN neurons. The effects of phorbol esters were antagonized by the specific PKC blockers bisindolylmaleimide and calphostin C. Although modulation of the synaptic potentials appears to be mediated by presynaptic PKC, the differential effects of PDAc on the fEPSP and the population spike also suggest the involvement of postsynaptic PKC and postsynaptic targets. These experiments demonstrate that protein kinase C is capable of profoundly modulating synaptic transmission at parallel fiber synapses in the DCN.

Implantation of the Lateral Cochlear Wall for Auditory Nerve Stimulation

Although cochlear implants now regularly achieve gratifying results, traditional intrascalar implants have certain limitations. Extraluminal implants may offset some of these problems by accessing neurons subserving a wider tonotopic range, avoiding intracochlear insertion trauma, and offering alternatives when cochlear obliteration is present. We have investigated the utility of a lateral cochlear wall implant in a normal‐hearing cat model with implants at the middle and basal turns, and found successful activation of the auditory nerve at thresholds of 28.1 and 40.6 μA, respectively. No adventitial stimulation of the facial nerve was noted within the dynamic range. Maximum responsiveness was observed with implants of the middle turn of the cochlea, an area that is not reliably approached with current intrascalar implants. These observations support and extend prior observations of the feasibility of extraluminal stimulation of the auditory nerve.

A fast, high precision and inexpensive analog to digital board for PC-AT or compatible

We describe a simple and inexpensive circuit for analog data acquisition with high speed and high resolution, for use in an IBM PC-AT or compatible. The circuit is suitable for a wide range of applications in electrophysiology. Features of the circuit include multichannel reading, programmable sampling rate, and direct memory access controlled dual buffering for continuous recording. A program written in the C programming language for control of data acquisition is also given.