Synaptic integration in dendrites: exceptional need for speed

Abstract

Some neurons in the mammalian auditory system are able to detect and report the coincident firing of inputs with remarkable temporal precision. A strong, low-voltage-activated potassium conductance (g(KL)) at the cell body and dendrites gives these neurons sensitivity to the rate of depolarization by EPSPs, allowing neurons to assess the coincidence of the rising slopes of unitary EPSPs. Two groups of neurons in the brain stem, octopus cells in the posteroventral cochlear nucleus and principal cells of the medial superior olive (MSO), extract acoustic information by assessing coincident firing of their inputs over a submillisecond timescale and convey that information at rates of up to 1000 spikes s(-1). Octopus cells detect the coincident activation of groups of auditory nerve fibres by broadband transient sounds, compensating for the travelling wave delay by dendritic filtering, while MSO neurons detect coincident activation of similarly tuned neurons from each of the two ears through separate dendritic tufts. Each makes use of filtering that is introduced by the spatial distribution of inputs on dendrites.

Figure 1. Octopus and MSO cells both detect coincidence in excitatory input

A, top panel, dendrites of octopus cells emanate from the rostral side of the cell body and spread across the tonotopic array of auditory nerve fibres where they are closely bundled as they pass from the ventral to the dorsal cochlear nucleus. The beginning of the axon is shown in red. Thus, cell bodies receive input from fibres tuned to the lowest frequencies (red) and the tips of dendrites receive inputs from fibres tuned to the highest frequencies (purple). (Cell is reproduced with permission from Golding et al. 1995.) Bottom panel, octopus cells detect coincident firing in groups of auditory nerve fibres (>60 in mice). Dendritic filtering makes octopus cells most sensitive to soma-directed sweeps of excitation that match the sweep of excitation produced by the cochlear travelling wave. B, top panel, MSO cells detect coincident firing of 2 to 5 ipsi- and 2 to 5 contralateral excitatory inputs tuned to similar low frequencies. The principal cells of the MSO are bipolar, with sparsely branching lateral and medial dendrites receiving inputs from ipsi- and contralateral sides, respectively. Tuning of MSO neurons is biased toward low frequencies. Bottom panel, the timing of MSO inputs at the soma reflects random differences in dendritic location. MSO neurons detect the coincidence in the average summed excitatory inputs from each side.

Figure 2. Responses to current reflect the presence of two voltage-sensitive conductances, g_h and g_KL

A, whole-cell recordings from an octopus and an MSO cell show the influence of g_h and g_KL. Responses are to a family of current pulses (−2.5 to +2.5 nA in 0.4 or 0.5 nA increments). Large depolarizing currents evoke a single action potential followed by a small steady depolarization, reflecting the shunting and hyperpolarizing influence of g_KL. Action potentials recorded at the cell body are small. Hyperpolarizing current pulses evoke a large hyperpolarization that sags toward rest, reflecting the slowly developing depolarization by g_h. Octopus cells often fire at the offset of hyperpolarizing pulses. Single exponentials fit to voltage changes within 3 mV of rest have time constants <0.5 ms. (Traces from octopus cells are adapted from Fig. 2 of Golding et al. 1999, with permission.) B, the voltage–current relations of the octopus and MSO cells in A from rest are similar. Input resistances near rest are <5 MΩ. C, summary of measurements of the voltage sensitivity of g_h and g_KL in octopus (red) and MSO (blue) cells measured under similar conditions (Bal & Oertel, 2000; Bal & Oertel, 2001; Mathews et al. 2010; Khurana et al. 2012). At the resting potential, opposing currents with opposite voltage sensitivity are partially activated.

Figure 3. Octopus and MSO cells require rapid depolarization to fire

A, octopus and MSO cells are capable of responding to suprathreshold EPSPs at frequencies of >500 Hz. (Trace from octopus cell is adapted from Fig. 8 of Golding et al. 1995, with permission.) B, the activation of g_KL by 1.2 ms ramps of current prevents firing when depolarization is too slow, conferring a dependence of firing on a threshold rate of depolarization. Octopus and MSO cells integrate depolarization over a time window of about 1 ms (shaded areas). (Data on octopus cells are adapted from Fig. 3 of Ferragamo & Oertel, 2002; Michael T. Roberts provided the unpublished recording from the MSO cell.) C, plot of the amplitude of the response to current ramps shown in B shows a jump when they reach threshold (Δ). Plot also shows responses to 1.0 ms (O) and 1.4 ms (□) ramps to the same current levels. The octopus and MSO cells in B have rate of depolarization thresholds between 10 and 13 mV ms⁻¹. (Data in C from octopus cell is from Fig. 3 of Ferragamo & Oertel, 2002, with permission. MSO data are from the same cell as in B.)