Periodic neuronal activity has been observed in various areas of the brain, from lower sensory to higher cortical levels. Specific frequency components contained in this periodic activity can be identified by a neuronal circuit that behaves as a bandpass filter with given preferred frequency, or best modulation frequency (BMF). For BMFs typically ranging from 10 to 200 Hz, a plausible and minimal configuration consists of a single neuron with adjusted excitatory and inhibitory synaptic connections. The emergence, however, of such a neuronal circuitry is still unclear. In this letter, we demonstrate how spike-timing-dependent plasticity (STDP) can give rise to frequency-dependent learning, thus leading to an input selectivity that enables frequency identification. We use an in-depth mathematical analysis of the learning dynamics in a population of plastic inhibitory connections. These provide inhomogeneous postsynaptic responses that depend on their dendritic location. We find that synaptic delays play a crucial role in organizing the weight specialization induced by STDP. Under suitable conditions on the synaptic delays and postsynaptic potentials (PSPs), the BMF of a neuron after learning can match the training frequency. In particular, proximal (distal) synapses with shorter (longer) dendritic delay and somatically measured PSP time constants respond better to higher (lower) frequencies. As a result, the neuron will respond maximally to any stimulating frequency (in a given range) with which it has been trained in an unsupervised manner. The model predicts that synapses responding to a given BMF form clusters on dendritic branches.
Periodic spiking neuronal activity is ubiquitous in the brain, from afferent sensory pathways (Krishna & Semple, 2000; Rees & Palmer, 1989; Langner & Schreiner, 1988; Rees & Møller, 1983, 1987) up to the cortex (Las, Stern, & Nelken, 2005; Fries, Reynolds, Rorie, & Desimone, 2001; Langner, 1992; Gray, König, Engel, & Singer, 1989). In the mammalian auditory brainstem, this activity reflects the periodicity of external stimuli and thus carries valuable information about the environment (Highley & Contreras, 2006; Joris, Schreiner, & Rees, 2004; Krishna & Semple, 2000; Rees & Palmer, 1989; Langner & Schreiner, 1988; Schreiner & Langner, 1988; Speck-Hergenröder & Barth, 1987; Rees & Møller, 1983, 1987). In contrast, oscillatory activity observed in higher-level brain areas, such as the cortex and hippocampus, does not originate directly from sensory inputs. The origin of these oscillations is not fully understood, but they are known to exhibit a spread range of frequencies, including the beta, gamma, and theta rhythms. These rhythms are hypothesized to play a role in the formation of mental objects (Shinn-Cunningham & Wang, 2008; Roelfsema, 2006; Gray et al., 1989) and attention (Bidet-Caulet et al., 2007; Knudsen, 2007; Roelfsema, 2006; Gonzalez Andino, Michel, Thut, Landis, & Grave de Peralta, 2005; Eggert & van Hemmen, 2002; Fries et al., 2001); the extent of their possible functions is an active topic of research (Banerjee & Ellender, 2009). At the scale of neuronal microcircuits, extracting information about the frequencies contained in the spiking activity may be an important part of spike-based computations.
Here we examine the tuning of a neuronal bandpass filter, that is, neurons that respond maximally when their stimulating inputs comprise a given periodicity. Recent findings have demonstrated the importance of inhibition during the critical period in the functional maturation of auditory pathways (Dorrn, Yuan, Barker, Schreiner, & Froemke, 2010). We analyze here a scheme where frequency selectivity arises from the activity-dependent plasticity of feedforward synaptic connections. Thus, we exclude the alternative approach where individual neurons themselves have frequency preference arising from specific membrane dynamics (Large & Crawford, 2002; Izhikevich, 2001). Rather, we consider a configuration with both excitatory and inhibitory incoming connections that allow frequency discrimination by selection of synaptic delays (Grothe, 1994) and time constants of the postsynaptic response (Bürck & van Hemmen, 2009; Nelson & Carney, 2004). Another alternative is frequency selection by coincidence detection using only excitatory synapses (Friedel, Bürck, & van Hemmen, 2007; Meddis & O'Mard, 2006; Licklider, 1951). Such a scheme has been used successfully with an ad hoc Hebbian learning rule (Grigorév & Bibikov, 2010). This will not be explored here: within the excitatory-inhibitory setup, we explain how synaptic plasticity can train a neuron to perform frequency selectivity in an unsupervised fashion.
To illustrate the general principles underlying frequency selectivity here, we focus on the auditory pathway in the midbrain, which exhibits a tonotopical organization that encodes the amplitude modulation of sound stimuli (Krebs, Lesica, & Grothe, 2008; Krishna & Semple, 2000). This means that the topological distribution of the network activity depends on the stimulating frequencies, thus creating a functional mapping of the input signals. Experimental observations in various animals have shown that a majority of best modulation frequency (BMF) lies in the range between 10 and 100 Hz (Krishna & Semple, 2000; Langner & Schreiner, 1988; Rees & Møller, 1983, 1987; Rees & Palmer, 1989). It turns out that this frequency range corresponds to the synaptic temporal properties found across many brain areas, that is, time course and delays in the order of milliseconds. With such “fast” timescales, rate-based plasticity mechanisms (Sejnowski, 1977; Bienenstock, Cooper, & Munro, 1982) cannot be used to train our amplitude modulation recognition system as they cannot capture the corresponding fine spike-time information.
Instead, spike-time-dependent plasticity (STDP) appears to be appropriate for generating neuronal specialization relying on such rapidly modulated signals (Gerstner, Kempter, van Hemmen, & Wagner, 1996). STDP is an implementation of Hebbian and anti-Hebbian learning at the synaptic level. It has been observed in various areas of the brain (Caporale & Dan, 2008; Dan & Poo, 2006), in particular, in the auditory brainstem (Tzounopoulos, Kim, Oertel, & Trussell, 2004; Tzounopoulos & Kraus, 2009; Bender & Trussell, 2011). The resulting learning dynamics can lead to the emergence of functional pathways depending on the fine temporal structure of input spike trains and has been the subject of numerous studies, mostly for excitatory synapses (Gilson, Burkitt, Grayden, Thomas, & van Hemmen, 2009; Gütig, Aharonov, Rotter, & Sompolinsky, 2003; Senn, 2002; Song, Miller, & Abbott, 2000; Kempter, Gerstner, & van Hemmen, 1999). Here, however, the focus is on STDP for inhibitory synapses (Woodin, Ganguly, & Poo, 2003; Haas, Nowotny, & Abarbanel, 2006). Although STDP has been used in a variety of setups with many different input signals (Roberts & Bell, 2000; Song & Abbott, 2001; Froemke & Dan, 2002; Cateau, Kitano, & Fukai, 2008; Lubenov & Siapas, 2008; Masquelier, Guyonneau, & Thorpe, 2008), its interplay with oscillatory neuronal input has just begun to be addressed (Scarpetta, Zhaoping, & Hertz, 2002; Pfister & Tass, 2010).
In the auditory system, previous studies have shown how STDP can organize excitatory synapses to generate a neuronal map that detects interaural time differences (ITDs; Leibold & van Hemmen, 2005; Leibold, Kempter, & van Hemmen, 2002; Gerstner et al., 1996). In such a setting, STDP modifies the synaptic strengths, which in turn affect the neuronal response to inputs, and this then takes effect on the learning. Among a population of synapses with various delays, STDP can select those corresponding to ITDs conveyed by the input spike trains. Dynamically, neurons that become selective are driven by increasingly stronger synapses, and this phenomenon self-reinforces. Consequently, the span of delays determines the range of ITDs that can be represented in the resulting synaptic structure.
In this letter, we take inspiration from these previous studies to obtain similar learning dynamics in the case of periodic input spike trains and plastic inhibitory synapses while excitatory connections remain fixed. We build our work on a previous study (Bürck & van Hemmen, 2009) that showed how a neuronal bandpass filter is tuned by the time constants and delays that determine the postsynaptic potentials (PSPs) in the case of feedforward excitatory and inhibitory connections that balance each other. In our model, the PSP time constants and delays (in addition to the synaptic weight) describe the variation of the soma potential induced by each presynaptic pulse. As in the case of ITDs, synaptic delays play a prominent role in determining the competition among synapses. We focus on the STDP-based selection process of synapses for a single neuron depending on the input spike trains that convey a given frequency through an oscillatory modulation of the spiking rate. As a first step toward obtaining an equivalent to a tonotopic map for BMFs, we examine the situation where a postsynaptic neuron responds maximally to the training frequency that is presented to it during a learning epoch, as compared to other frequencies. In other words, the training frequency should coincide with the BMF of the neuron after learning. However, the problem turns out to be more complex for frequency selectivity than for ITD selectivity. This follows because the frequency response of neurons is not all-or-nothing as with coincident detection for ITDs. We investigate conditions on the delays and PSP time constants that allow this unsupervised closed-loop learning scheme for any training frequency within a given range (here, from 20 to 100 Hz).
This letter has three parts. The following section presents a mathematical framework that describes the learning dynamics of feedforward inhibitory connections arising from pairwise STDP. Note that this framework can be straightforwardly transposed to study the converse situation of fixed inhibitory and plastic excitatory connections. In section 3, we derive conditions on the synaptic delays and PSP time constants under which a neuron becomes selective (i.e., it shows a BMF) to the frequency it is trained with. Finally, we present numerical simulations that support our theoretical predictions and compare them with experimental observations.
2. Mathematical Framework for a Single Output Neuron
This section presents the theory required to examine the learning dynamics that leads to frequency selectivity. The analysis focuses on a single output neuron that receives oscillatory input spike trains through ME excitatory fixed synapses and MI plastic inhibitory synapses, as illustrated in Figure 1A. Plastic inhibitory synapses are modified using the STDP model that will be detailed in section 2.1. During the learning process, all input neurons are driven by an oscillation with a fixed frequency f. The resulting correlation structure and its influence on the learning dynamics will be analyzed in section 2.2. In section 2.3 we introduce a specific neuron model, which is needed to solve the learning dynamics in a closed form. To keep the analytical calculations simple, we examine the idealized case of a single excitatory synapse (ME=1) and an arbitrary number of inhibitory synapses with distinct properties, that is, distinct delays and PSP time constants. Later in the numerical simulations, these individual synapses are replaced by populations of synapses.
2.1. Model of Spike-Timing-Dependent Plasticity.
Throughout this letter, we use the pairwise additive STDP model (Kempter et al., 1999) that captures the crucial dependence about spike timing in synaptic plasticity observed in experimental studies (Markram, Lübke, Frotscher, & Sakmann, 1997; Bi & Poo, 1998) but does not account for other properties such as the weight dependence or interactions between more than two spikes (Sjöström, Turrigiano, & Nelson, 2001; Gütig et al., 2003; Appleby & Elliott, 2006; Morrison, Diesmann, & Gerstner, 2008). In this way, we focus on weight specialization in the process of selecting synapses and leave aside issues about the saturation of individual weights. Additive STDP tends to separate synaptic weights into a bimodal distribution, which appears suitable for modeling the development of neuronal circuitry during the critical period for audition or vision, after which depressed synapses would be eliminated. Homeostatic stability for the weight dynamics is achieved by using additional rate-based plasticity terms (Kempter et al., 1999).
Importantly, STDP occurs at the synaptic site in our model, which means that propagation delays are taken into account and affect the timing of pre- and postsynaptic spiking activity “felt” by the synapse (Senn, Schneider, & Ruf, 2002). For the plastic synapse k from input neuron k to the output neuron (subscript “out”), we denote the axonal delay by dak to account for the axonal transmission and neurotransmitter diffusion. Likewise, the dendritic delay ddk models the propagation of PSPs along the dendritic tree toward the soma, as illustrated in Figure 1B. We further assume that for each synapse, the backpropagation of action potentials toward the synapse, which plays a role in synaptic plasticity, also corresponds to ddk. This assumption is reasonable for a passive membrane and simplifies the notation, but it turns out not to be critical in the calculations. In this way, a presynaptic spike fired by input neuron k at time tk will affect the synapse k at time tk+dak; likewise, the effect of a spike fired by the postsynaptic output neuron at time tout on the synapse will start at time tout+ddk.
The above calculations require T to be much larger than the timescale of the neuronal activation mechanisms but much smaller than . This ensures that the variables , , and Fk are well defined, independent of the choice of a particular neuron model. (Details can be found in Gilson et al., 2009.)
2.2. Oscillatory Inputs and Spike-Time Correlation Structure.
When a neuron is stimulated by oscillatory inputs with a given frequency spectrum, the input-to-neuron covariance Fk in equation 2.4b is affected by the input-to-input covariances Ckl. In order to evaluate the synaptic filtering that transforms Ckl into Fk, we now choose a concrete neuron model.
2.3. Poisson Neuron Model.
We now analyze the mathematical formulation of the learning dynamics in section 2 to arrive at a general understanding of the dynamical principles to drive the emergence of frequency selectivity in a single neuron using a simplified configuration. More precisely, we examine conditions on the synaptic properties such that the BMF of the trained neuron corresponds to the training frequency, as detailed below. Then we present simulation results using a more realistic setting where a single neuron is tuned appropriately in order to verify the theoretical predictions.
Our scheme articulates three steps. First, learning must depend on the frequency of the training signal. The axonal and dendritic delays primarily determine how the synapses compete via STDP and, in particular, which ones are the “winners.” Second, the selected synapses give rise to frequency selectivity, that is, the trained neuron responds maximally to a specific frequency—its BMF. The BMF is determined by the PSP time constants and the delays of the winner synapses (Bürck & van Hemmen, 2009). Third, the BMF resulting from learning must be the same as the training frequency. Therefore, we need to match the distributions of PSP time constants and delays associated with the synapses. The following analysis describes the effect of these different PSP time constants and delays on the learning, which results in a complex relationship between the training frequency and BMF.
3.1. Mathematical Analysis of STDP Dynamics and Neuronal Frequency Response.
Now we detail the procedure used to evaluate any arbitrary configuration of PSP time constants and delays. As we explained earlier, the evaluation consists of three sequential steps, which are performed for all training frequencies in a given range:
We examine which (single) synapse wins the STDP competition.
The winner synapse determines the frequency responsiveness of the neuron, which gives its BMF.
We evaluate how close the BMF is to each training frequency in the considered range.
In contrast to the scheme detailed here, the problem of tuning parameters to detect ITDs mainly consists in performing step 1—matching the synaptic delays and input ITDs to obtain the desired learning outcome. Since the trained neuron responds or not depending on the relative timing of two inputs (from the two ears), this means that steps 2 and 3 are much simpler in the case of ITDs.
3.2. Dendritic Location and PSP Properties.
In our model, the shape of the STDP learning window W(u) is identical for each synapse. However, propagation delays along the dendrite shift the STDP curve, as was observed experimentally (Letzkus, Kampa, & Stuart, 2006, Fig. 8). Here both synaptic delays shift W(u) according to their difference dak−ddk (see equation 2.1). This can strongly affect the weight specialization (Leibold et al., 2002; Senn et al., 2002; Lubenov & Siapas, 2008; Gilson, Burkitt, Grayden, Thomas, & van Hemmen, 2010), as described here by FWk in equation 3.3. In parallel, the time constants associated with the somatic PSP kernels as well as also shape the response in frequency of the output neuron (Bürck & van Hemmen, 2009). Specifically, we postulate that the time constants for inhibitory PSPs depend on the distance to the soma, as schematically represented in Figures 3A and 3B. Before going further with the frequency selectivity, we take a closer look at the biological relevance of this assumption.
3.3. Tuning Synaptic Parameters to Obtain Frequency Selectivity.
Following the results in Figure 3, our model abstracts the physiological property that proximal synapses have shorter dendritic delays and PSP time constants than distal ones. This leaves a degree of freedom in tuning the axonal delays. Now we examine how to choose the latter together with the synaptic heterogeneity in order to obtain the desired learning dynamics. We focus on a range of training frequencies between 10 and 100 Hz, with only multiples of 5 Hz to simplify the analysis. For illustration purposes, we consider a pool of 100 synapses and tune the synaptic delays dak and ddk as well as the time constants for . Our choice of alpha functions for the PSP kernels in equation 2.8, which are described by a single time constant, also keeps the optimization as simple as possible. With such frequencies, appropriate parameters range between 0 and 10 ms, which is physiologically plausible, as shown earlier. We use a random exploration to obtain suitable sets of parameters, where the dendritic delays and PSP time constants vary jointly in a similar manner to Figure 3D.
Once the synaptic parameters are fixed, we can evaluate the effect of STDP via the learning integral FWk in equation 3.3. For the learning scheme to work efficiently, spike effects should be significant as compared to the rate effects in equation 2.3. This requires that the Fourier transform of W have significant power (as given by the absolute value) in the range of frequencies considered as compared to the integral value that corresponds to the value of the Fourier transform in f = 0, namely, , as illustrated in Figure 4. Likewise, the training neuronal filter will be more selective if each possible expression for in equation 3.7 has a clear maximum, and this for all possible potentiated synapse (without considering the relationship between and yet). Two examples are plotted in Figure 4 (see the dashed gray lines).
Synapses compete with each other, and those with indices k corresponding to larger values of FWk will be maximally potentiated by STDP. We thus consider the curves of for each training frequency and, in a winner-take-all fashion, we retain only the “best” synapse that corresponds to the maximum. In Figure 5A, the corresponding curves are plotted for three values of . In order to obtain effective frequency-dependent learning, curves for distinct training frequencies, should have a clear maximum for different synapse indices k. Varying dendritic and axonal delays in opposing fashion (i.e., the former increasing with k while the latter decreases) leads to strong selectivity, as this implies large delay differences dak−ddk across synapses. The relation between the training frequency and the best synapse is plotted in Figure 5B. Higher training frequencies select smaller synapse indices , corresponding to longer PSP time constants and dendritic delays.
From the indices , we obtain the frequency response curves corresponding to , which are plotted in Figure 5C. Their respective maxima give the BMF . As shown in Figure 5D, it is possible to find parameters such that the training frequency and BMF match closely in the range 20 to 90 Hz. In other words, we aim to find a suitable distribution of PSP time constants and delays that leads to the theoretical unsupervised scheme in which the neuronal bandpass filter tunes itself to its training frequency.
3.4. Numerical Simulation of a Single Neuron.
The procedure in the previous section has led us to choose the parameters in Table 1, which we verify using numerical simulation. In order to find those parameters, we simply performed an exploration of randomly chosen sets of parameters within a given range (between 0 and 10 ms) and kept the best ones. We constrained the search to configurations where the excitatory synapses have faster time constants than the inhibitory synapses (see Figure 3). It was found that an equidistant distribution of the parameters between two extremal values (e.g., a=0.8 and b=3.8 ms for ddk in Table 1) requires more fine tuning. Instead, we use nonuniformly distributed parameters for the inhibitory synapses in order to give more synapses with short than large time constants (see Figure 5E). Rather than a+(b−a)(k−1)/(MI−1) for , we use a+(b−a)(k−1)1.6/(MI−1)1.6. The specific value 1.6 has been chosen for illustrative purposes only here. When the PSP time constants and dendritic delays increase almost linearly as in Figure 3D, this situation corresponds to a larger density of proximal synapses compared to distal ones.
|Number of synapses ME||50|
|Dendritic delays dE||0.8 ms|
|Time constants||0.9 ms|
|Number of synapses MI||100|
|Dendritic delays ddk||0.8–3.8 ms|
|Axonal delays dak||4.8–3.3 ms|
|Time constants||1–9 ms|
|Number of synapses ME||50|
|Dendritic delays dE||0.8 ms|
|Time constants||0.9 ms|
|Number of synapses MI||100|
|Dendritic delays ddk||0.8–3.8 ms|
|Axonal delays dak||4.8–3.3 ms|
|Time constants||1–9 ms|
To maintain mathematical tractability in our prior calculations, we have made a number of assumptions that do not hold in simulations. First, the homeostatic stability is qualitatively satisfied, but the corresponding equilibrium value significantly differs from in equation 3.2. Two factors explain such discrepancies: the nonlinearity of the Poisson neuron for negative soma potential (i.e., when inhibition overpowers excitation) and the presence of spike-time correlations that are neglected in the derivation of . Because input-to-neuron correlations depend on the input frequency (see equation 2.10b), the homeostatic equilibrium value differs for different training frequency , meaning different levels of balance between inhibition and excitation. In our simulations, we observed a stronger response in firing rate for larger training frequencies , which arises because the effect of STDP vanishes for large frequencies (see Figure 4) and thus leads to a weaker potentiation of inhibitory weights. Second, in order to predict the frequency response of the trained neuron, we have considered the ideal winner-take-all situation where a single synapse is selected by STDP (i.e., unique values for the time constant and delays). Together, these two factors mean that the calculation in equation 3.6 only approximates the neuronal filtering after the STDP learning in the more realistic situation that is simulated. The theory, however, still provides sufficient information on the trends of our learning system to determine the PSP properties and delays such as to obtain the desired unsupervised learning outcome.
Figure 6A shows a typical evolution of the weights when the neuron is excited by a single training frequency (here, Hz). A subgroup of synapses with similar parameters is potentiated while the remainder is depressed in a winner-share-all fashion. With our choice of learning rate , a typical STDP update corresponds to of the total range, as weights are constrained between the bounds 0 and 0.1. Here the neuron is trained for 1000 s, which corresponds to about spikes per synapse. Despite the weight dynamics being significantly noisy, the functional weight structure remains relatively stable after 600 s. For different training frequencies, distinct subsets of synapses are selected, as shown in Figures 6B to 6D, for the training frequencies , 50, and 70 Hz; the arrow indicates the index of the best synapse predicted by the theory.
Now we measure the frequency response via the neuronal firing rate (averaged over 50 s) when presenting successively all test frequencies between 0 and 100 Hz (with steps of 5 Hz) while freezing the weight structure obtained after 1000 s of STDP learning. The corresponding curves averaged over 10 trials are represented in Figure 7A for the same frequencies as in Figure 6, namely, , 50, and 70 Hz. The error bars represent the standard deviation of the frequency responses, which indicate the high variability across the 10 trials. The summary for all training frequencies from 20 to 90 Hz is illustrated in Figure 7B, where the white circles represent the maximum for each curve similar to those in Figure 7A. The background color for the “column” corresponding to each training frequency corresponds to the intensity of the frequency response curve: A darker shading indicates a stronger response, whose maximum corresponds to the white circle; note that the curve for each has been rescaled independent of the other training frequencies. In addition to the natural averaging to predict the BMF represented by the circles, we evaluate another estimator for the BMF: we interpolate the frequency response for each trial using a polynomial of degree 4 and then determine the maximum. The error bars indicate the mean of those maxima averaged over all trials and their standard deviation. Our results satisfactorily agree with the theoretical predictions (dashed gray curve) for the range between 30 and 70 Hz, but they become poorer beyond this range. We stress that the neuronal system studied here is very noisy due to our model of inputs that does not contain any other temporal correlation apart from that arising from the oscillatory firing rates and to the stochastic nature of the Poisson neurons. The results presented here provide strong support for the hypothesis that STDP is capable of producing frequency selectivity in this context that assumes minimal spike-time information.
We have examined the unsupervised emergence of frequency selectivity when STDP trains a single neuron. Synaptic competition arises from the interaction of STDP, the inhomogeneous postsynaptic responses, and the periodicity of the input spike trains. In a simple configuration where the neuron has fixed excitatory and plastic inhibitory synapses (see Figure 8), this weight selection scheme causes the neuron to become maximally responsive to a particular input frequency, termed its BMF. Our mathematical framework allows the derivation of conditions on the synaptic parameters such that the BMF after learning matches the training frequency presented to the neuron, and this for a range of training frequencies (20–90 Hz).
Our results aim to shed light on the tuning of neuronal circuitry required to perform a frequency decomposition of input signals. Our theoretical contribution lies in analyzing the interaction between oscillatory spiking activity and STDP. First, we have shown how oscillatory spike trains induce temporal correlations and how STDP captures this short-time spiking information, in particular, the effect of shifting the STDP curve by means of delays (Morrison et al., 2008; Gilson et al., 2010). This has allowed us to determine conditions on the PSP time constants and delays under which STDP results in neuronal frequency selection. Note that excitatory synapses have faster time constants and delays than inhibitory synapses. With the STDP model used here that results in homeostasis, synapses compete with each other, which means that only the maximally potentiated synapses (when evaluating the spike-based terms involving the convolution with the learning window W) will be effectively potentiated. In the end, the synaptic structure obeys a detailed balance as described by Vogels et al. (2011) that is determined by the training frequency. Second, the analysis of the weight dynamics is similar to that used in other applications of STDP, such as auditory ITD processing (Leibold & van Hemmen, 2005; Leibold et al., 2002; Gerstner et al., 1996) or selection of the “effective” synaptic delay (Senn et al., 2002), but the desired frequency selectivity implies further constraints on the parameters compared to those previous studies. Although not formulated as an STDP rule, the Hebbian learning rule that Grigorév and Bibikov (2010) used favors excitatory synapses whose delays correspond to the periodicity of the presented signal. That configuration is the converse of our proposed scheme based on inhibitory STDP. Importantly, our version of STDP is completely local, as compared to many previous models. Relying on similar dynamics, another recent theoretical study investigated how to desynchronize a recurrent neuronal network using STDP on excitatory connections, in the context of deep-brain stimulation (Pfister & Tass, 2010). There the goal was to use periodic stimulation so that STDP weakens the recurrent feedback in the network (by shifting the fixed point of the synaptic dynamics). However, that study did not consider inhomogeneous synaptic responses, and although the resulting STDP dynamics was frequency dependent, the input frequency did not play a significant role in the competition between synapses there. Note also that beyond the application to frequency learning, the equations derived here can be straightforwardly adapted to study other situations where inhomogeneous synaptic properties interplay with STDP.
In our learning neuronal system, both dendritic delays and PSP time constants were assumed to increase with the distance to the soma (see Figure 5E), which is supported by experimental observations (Miles, Toth, Gulyas, Hajos, & Freund, 1996). Assuming a passive dendrite, we have shown that the temporal range assumed here is biologically plausible. Actually, the cable equation, 3.9, requires strong assumptions, such as an infinite length for the dendrite and constant diameter (Koch & Segev, 1998). A particular point is that as dendrites become thinner toward their extremity, the spatial constant decreases, meaning that shorter lengths may be sufficient compared to those calculated in Figure 3D in a more realistic configuration. We also did not take into account any specific ion channel or neurotransmitter. The solution presented in section 3.4 is not unique, so alternative location-dependent distributions of synaptic properties may be matched adequately. Nevertheless, the general upshot is that more proximal and more distal synapses specialize to high and low frequencies, respectively, as illustrated in Figures 8A and 8B. This relationship between the functional response of synapses (corresponding BMF) and their location on dendrites is the main prediction of our theory. It contrasts with experimental observations in the auditory cortex that synapses responding to frequencies above 200 Hz (i.e., related to the postcochlear tonotopic organization) do not exhibit a clustered organization on dendrites (Chen, Leischner, Rochefort, Nelken, & Konnerth, 2011).
In order that the postsynaptic neuron tunes its BMF to the stimulating frequency, axonal delays on the presynaptic side must be adjusted to the dendritic delays and PSP time constants on the postsynaptic side, as explained in section 3.3. (If, instead, we only request the postsynaptic neuron to specialize to some BMF, weaker constraints that potentiate clustered synapses on the dendritic tree may be sufficient.) It remains to be understood what mechanisms may lead to this coordination of dendritic and axonal delays. A possible candidate is the experimentally observed modification of delays during plasticity (Lin & Faber, 2002); a full study of the combined dynamics is left to subsequent work. Another interpretation of the axonal delay is a phase shift of the oscillatory signal at the inhibitory synapses with respect to that at the excitatory synapses. For our choice of parameters, these correspond to small phase delays for the inhibitory inputs that depend on the training frequency, as illustrated in Figure 8C. Finally, similar results can be obtained using our theory for a bimodal “asymmetric” STDP learning window, that is, potentiation when the effect of the presynaptic spike precedes that of the postsynaptic spike, and depression otherwise, which has also been experimentally observed for inhibitory synapses (Haas et al., 2006). However, it was found that these many opposing weight updates generate in practice additional noise in the synaptic dynamics, which dramatically weakens the weight specialization. Therefore, we present results only for the symmetric learning window in Figure 1.
A further step is to obtain a map of neurons similar to the single neuron trained here in order to perform a frequency decomposition of the modulation frequency conveyed by the input spike trains. By this, we mean a topographically organized specialization such that neighboring neurons have similar BMF. In this respect, our proposed scheme differs from the dynamics of some other STDP models (Izhikevich & Desai, 2003; Burkitt, Meffin, & Grayden, 2004; Pfister & Gerstner, 2006), whose dynamics also depends on the output frequency of the postsynaptic neuron. In those models, a higher training frequency would be systematically favored because shorter interspike intervals lead to stronger potentiation. This contrasts with our study based on the tuning of synaptic filtering, which allows low frequencies to be learned as well. A more complete model of the auditory pathway in the midbrain would also incorporate details of realistic inputs coming from the cochlea. The cochlea mechanically decomposes sound vibrations into bands of high frequencies, namely, from 0.5 to 20 kHz. Outgoing fibers thus convey high-frequency-specific spike trains that also comprise modulating frequencies (as studied in this letter) and excite specific subregions of the auditory midbrain, in this way forming a tonotopic map. Two types of correlations are thus superimposed in the input spike trains coming from the cochlea, but the correlations related to high frequencies do not interact with STDP as in our scheme (this would require submillisecond synaptic activation timescales). Therefore, our learning scheme appears plausible in a more elaborate model to obtain both BMF and tonotopic neuronal mapping. Experiments have shown how the neuronal response to high frequencies is shaped by the maturation of inhibitory circuitry (Dorrn et al., 2010) and modified following specific stimulation protocols (Dahmen, Hartley, & King, 2008). Our model predicts similar changes in the low-frequency range (e.g., shifting the BMF toward a different stimulating frequency).
Beyond neuronal identification of amplitude modulations within one cochlear frequency channel, our study has more general implications for brain areas that exhibit periodic spiking activity, such as the cortex and hippocampus. It suggests that the inhomogeneous postsynaptic responses and spike-based plasticity form a natural substrate for neurons to extract frequencies conveyed by spike trains. Along a similar line, a neuron was successfully trained by triplet-STDP to detect stimulus velocities of moving bars in a model visual field (Gjorgjieva, Clopath, Audet, & Pfister, 2011). The speed of the bar introduces delays in the inputs, and the synaptic competition is equivalent to selecting delays in order to shape the global postsynaptic response with a preference to a given velocity. In summary, the location-dependent properties of somatic PSPs in Figure 3, which can also be supplemented by location-dependent STDP as was observed for excitatory synapses (Froemke, Poo, & Dan, 2005; Letzkus et al., 2006; Froemke, Letzkus, Kampa, Hang, & Stuart, 2010), appears to be a genuine learning device to extract complex spiking information at a short timescale. Nonlinearities in the PSP integration (London & Häusser, 2005) may play a further role by shaping the input-to-neuron correlations. Together, this theoretical work stresses the importance of incorporating morphological features of dendrites for learning and computation with spikes.
We are grateful to the reviewers for comments that greatly improved the manuscript. M. B. benefited from a stay at Tomoki Fukai's Lab for Neural Circuit Theory (Riken Brain Science Institute, Japan).
Matthieu Gilson and Moritz Bürck contributed equally to this letter.