Asynchronous inputs alter excitability, spike timing, and topography in primary auditory cortex

Abstract

Correlation-based synaptic plasticity provides a potential cellular mechanism for learning and memory. Studies in the visual and somatosensory systems have shown that behavioral and surgical manipulation of sensory inputs leads to changes in cortical organization that are consistent with the operation of these learning rules. In this study, we examine how the organization of primary auditory cortex (A1) is altered by tones designed to decrease the average input correlation across the frequency map. After one month of separately pairing nucleus basalis stimulation with 2 and 14 kHz tones, a greater proportion of A1 neurons responded to frequencies below 2 kHz and above 14 kHz. Despite the expanded representation of these tones, cortical excitability was specifically reduced in the high and low frequency regions of A1, as evidenced by increased neural thresholds and decreased response strength. In contrast, in the frequency region between the two paired tones, driven rates were unaffected and spontaneous firing rate was increased. Neural response latencies were increased across the frequency map when nucleus basalis stimulation was associated with asynchronous activation of the high and low frequency regions of A1. This set of changes did not occur when pulsed noise bursts were paired with nucleus basalis stimulation. These results are consistent with earlier observations that sensory input statistics can shape cortical map organization and spike timing.

Introduction

Under appropriate conditions, adult cortical sensory representations can be remodeled through learning (Jenkins et al., 1990, Recanzone et al., 1992a, Recanzone et al., 1993). Experiments conducted in the visual, somatosensory, and auditory systems have provided compelling evidence that different sensory input patterns can lead to distinctly different forms of cortical reorganization (Allard et al., 1991, Kilgard et al., 2002, Stryker and Strickland, 1984, Wang et al., 1995). Behaviorally relevant sensory and motor events are marked by increased activity in nucleus basalis (NB), which projects to the entire cortex and powerfully modulates plasticity (Conner et al., 2003, Kilgard and Merzenich, 1998b, Kilgard et al., 2001a, Weinberger, 1998).

Changes in neural connectivity and dynamics likely provide the biological basis for learning and memory (Kandel, 2001, Katz and Shatz, 1996). Synaptic connections typically follow correlation-based learning rules such that connections between neurons with correlated activity are strengthened and connections between uncorrelated neurons are weakened (Bi and Poo, 2001, Hebb, 1949, Stent, 1973). These changes in synaptic strength are often accompanied by changes in neural sensitivity and latency.

Observations from several cortical plasticity studies are consistent with the operation of correlation-based learning rules in vivo. Increasing input correlation via strobe rearing, whisker pairing protocols, or tactile discrimination training results in shorter latencies in visual and somatosensory cortices (Armstrong-James et al., 1994, Humphrey et al., 1998, Recanzone et al., 1992b). In contrast, decreasing input correlation via strabismus, monocular deprivation, or frequency discrimination training results in prolonged latencies in the visual and auditory cortices (Chino et al., 1988, Chino et al., 1983, Eschweiler and Rauschecker, 1993, Recanzone et al., 1993). Decreased response latencies were observed after a single tone was paired with nucleus basalis stimulation, while latencies were increased when seven different tones were independently paired with nucleus basalis stimulation (Kilgard et al., 2001a). In that study, we speculated that latency was decreased when map expansion drove a net increase in the correlated activity across A1 and latency was increased when tonal inputs were distributed across A1 in the absence of map plasticity. Collectively, these observations are compatible with the hypothesis that synaptic correlation-based learning rules have a significant impact on the expression of network level plasticity.

To confirm that a net decrease in input correlation induces a weakening of auditory cortical responses that is reflected by longer response latencies and reduced response strength, we exposed animals to tonal inputs designed to activate two non-overlapping neural populations at different times. These tones were paired with electrical activation of the nucleus basalis as in our earlier studies. Nucleus basalis stimulation paired with sensory input has been used extensively by several research groups to promote input guided cortical plasticity in the absence of behavior (Bakin and Weinberger, 1996, Edeline et al., 1994, Kilgard et al., 2001a, Metherate and Ashe, 1993, Rasmusson and Dykes, 1988). While nucleus basalis stimulation is an unnatural method for gating representational plasticity, this paradigm makes it possible to manipulate sensory statistics by delivering arbitrary input patterns without the need for time-consuming behavioral training or surgical procedures.

In the present study, we use this well-established technique to further explore how asynchronous activation directs plasticity in primary auditory cortex. We report that pairing randomly interleaved high and low frequency tones, which drove a net decrease in the correlation across the frequency map, with activation of neuromodulatory inputs led to map plasticity, decreased cortical excitability, increased spontaneous activity, and lengthened response latencies compared to naı¨ve controls. This set of changes did not occur when pulsed noise bursts were paired with nucleus basalis stimulation. Our results extend earlier observations that spatial and temporal cortical network organization can be shaped by distributed sensory inputs.