It is generally assumed that sensory input to the developing mammalian brain shapes the strength of synaptic connections and the membrane properties of neurons. However, although there is a wealth of experimental data showing that the gross aspects of neural pathways are dependent on sensory input, there is very little in vivo information on the effects of activity during development at the fundamental membrane and channel level, and much of our knowledge has come from neuronal culture systems. In addition to the familiar Hebbian plasticity, a prominent hypothesis to emerge from recent studies is the concept of homeostasis (Burrone & Murthy, 2003; Murphy, 2003; Turrigiano & Nelson, 2004; Thiagarajan et al. 2005). Homeostasis is commonly used to describe the attempt of a neuron to regulate its average firing rate to some ‘desired’ set point, in response to a change in the activity of the cell. The hypothetical homeostatic response may manifest itself as a change in the strength of synaptic inputs, and/or a change in the properties of the postsynaptic neuron. The basic premise of homeostasis is that, if the average firing rate of a neuron decreases, then the system will compensate by increasing the firing rate back to the ‘desired’ level by mechanisms that may include (1) increasing the strength of excitatory inputs, decreasing the strength of inhibitory inputs, or increasing the ratio of excitation to inhibition, and/or by (2) increasing the excitability of the postsynaptic neuron. (The opposite changes are proposed to occur as a consequence of an increase in the firing rate of a neuron.) In support of this hypothesis, a variety of experimental studies have shown that reduction in the firing rate of a neuron leads to an enhancement in the strength of excitatory inputs and a decrease in the strength of inhibitory inputs to that neuron. A change in synaptic strength may occur through a change in the total number of synaptic contacts, a change in presynaptic release, and/or a change in the postsynaptic response to neurotransmitter release. Distinct from homeostasis, Hebbian plasticity involves the strengthening of synaptic transmission through co-ordinated pre- and post-synaptic activity, and there is ample evidence for this process. Experimental manipulation of neuronal activity has led to a variety of effects, including changes in quantal size, attributed to changes in postsynaptic receptors (O'Brien et al. 1998; Turrigiano et al. 1998; Watt et al. 2000; Leslie et al. 2001; Kilman et al. 2002; Wierenga et al. 2005) or presynaptic changes in the amount of neurotransmitter packaged into vesicles (de Gois et al. 2005; Wang et al. 2005; Wilson et al. 2005), changes in quantal content without a change in quantal size (Paradis et al. 2001; Bacci et al. 2001), changes in synaptic size (Murthy et al. 2001) and changes in postsynaptic membrane properties (Daoudal & Debanne, 2003; Saar & Barkai, 2003; Zhang & Linden, 2003). Changes in neuronal excitability may occur through a variety of means, including a change in passive membrane properties (capacitance and resistance) or changes in voltage-activated currents (Daoudal & Debanne, 2003; Saar & Barkai, 2003; Zhang & Linden, 2003). In addition, morphological changes may alter the electrotonic architecture of the neuron. Experimental evidence has shown that changes in activity may alter the magnitude of voltage-activated sodium, potassium and calcium currents, and hyperpolarization-activated (Ih) currents (Daoudal & Debanne, 2003; Saar & Barkai, 2003; Zhang & Linden, 2003). For example, Desai et al. (1999) have demonstrated that, in visual cortex cultures, silencing of activity with TTX leads to a down-regulation of potassium currents and an up-regulation of sodium currents, with a resultant increase in cell excitability.
Thus, a variety of model systems have been used to demonstrate that activity can alter synaptic strength (both pre- and post-synaptically) and postsynaptic cell excitability. Some of these results are consistent with a so-called ‘homeostatic response’, and some are consistent with opposing mechanisms, such as ‘Hebbian’ strengthening of active synapses (Burrone & Murthy, 2003; Murphy, 2003). Furthermore, there is evidence that the response of a neuron to a change in activity may be different during development than in maturity (Burrone et al. 2002; Murphy, 2003). Despite these complications, recent studies, primarily using neuronal cultures, emphasize that the predominant response to a reduction in neuronal activity is a postsynaptic increase in quantal size (Turrigiano & Nelson, 2004). This raises the issue of what happens in the intact nervous system (Desai et al. 2002). This review highlights recent results from studies of the mammalian auditory system, in particular using deafness as a model of reduced or abolished sensory input during development. The results reveal that altered activity during development has multiple effects, including changes in excitatory and/or inhibitory synaptic transmission, and postsynaptic membrane properties. Furthermore, these changes may be different in different neuronal types, as previously described for long-term plasticity in the dorsal cochlear nucleus by Tzounopoulos et al. (2004). In addition, the results show that spontaneous activity during development is necessary for the proper formation of neural circuits (tonotopic maps) in central auditory nuclei.