Asynchronous inputs alter excitability, spike timing, and topography in primary auditory cortex
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.
Section snippets
Methods
The neural responses presented in this report were obtained from nine NB-stimulated rats and 15 naı¨ve controls. Detailed descriptions of experimental preparation and microelectrode mapping techniques can be found in previous publications (Kilgard and Merzenich, 1998a, Kilgard and Merzenich, 2002, Kilgard and Merzenich, 1998b, Kilgard et al., 2001a, Kilgard et al., 2001b) and are described in brief below.
Results
The physiological data presented here were obtained from over 1100 recording sites in primary auditory cortex from 24 rats. Neural responses from four rats exposed to tones separated by 2.8 octaves and five rats exposed to noise bursts were compared to 15 experimentally naı¨ve controls. The pattern of neural activity generated by randomly interleaved high and low frequency tones led to: (1) modest reorganization of the frequency map; (2) regionally specific decreases in cortical excitability;
Discussion
Numerous studies have demonstrated that altered sensory experience can reorganize cortical responses (Ahissar et al., 1992, Edeline, 1999, Engineer et al., 2004). Significant changes have been observed in receptive field size, cortical topography, response latency, spectrotemporal selectivity, response strength, and neuronal discharge coherence. Although it is clear that different behavioral paradigms generate different cortical changes, it has not been established what specific aspects of
Conclusions
Primary auditory cortex can be substantially reorganized in an experience-dependent manner. Results from a number of studies indicate that the spectral and temporal response properties of A1 neurons are shaped by the pattern of sensory inputs. The present study indicates that asynchronous high and low frequency tones paired with NB stimulation leads to cortical responses that are substantially slower, less sensitive, and less responsive. These inputs also induce modest reorganization of the
Acknowledgements
This work was supported by NIH/NIDCD R03-DC04534 (M.P.K.), an Individual NRSA Pre-Doctoral Award NIDCD F31-DC005285 (P.K.P.), and the American Academy of Audiology Student Investigator Award (P.K.P.). The authors thank Amber Cheney, Amanda Puckett, Wendy Dai, and Cherie Percaccio for assistance in animal training and colony management. We also acknowledge the constructive comments and suggestions of the reviewers.
References (51)
- et al.
Lesions of the Basal forebrain cholinergic system impair task acquisition and abolish cortical plasticity associated with motor skill learning
Neuron
(2003) Learning-induced physiological plasticity in the thalamo-cortical sensory systems: a critical evaluation of receptive field plasticity, map changes and their potential mechanisms
Prog. Neurobiol.
(1999)Timing-based LTP and LTD at vertical inputs to layer II/III pyramidal cells in rat barrel cortex
Neuron
(2000)- et al.
Distributed representation of spectral and temporal information in rat primary auditory cortex
Hear. Res.
(1999) - et al.
Pairing-induced changes of orientation maps in cat visual cortex
Neuron
(2001) - et al.
Cortical development and remapping through spike timing-dependent plasticity
Neuron
(2001) Physiological memory in primary auditory cortex: characteristics and mechanisms
Neurobiol. Learn Mem.
(1998)- et al.
Stimulus timing-dependent plasticity in cortical processing of orientation
Neuron
(2001) - et al.
Dependence of cortical plasticity on correlated activity of single neurons and on behavioral context
Science
(1992) - et al.
Reorganization of somatosensory area 3b representations in adult owl monkeys after digital syndactyly
J. Neurophysiol.
(1991)
An innocuous bias in whisker use in adult rats modifies receptive fields of barrel cortex neurons
J. Neurosci.
Induction of a physiological memory in the cerebral cortex by stimulation of the nucleus basalis
Proc. Natl. Acad. Sci. USA
Progressive degradation and subsequent refinement of acoustic representations in the adult auditory cortex
J. Neurosci.
Distributed synaptic modification in neural networks induced by patterned stimulation
Nature
Synaptic modification by correlated activity: hebb’s postulate revisited
Annu. Rev. Neurosci.
Cortical plasticity: from synapses to maps
Annu. Rev. Neurosci.
Effects of convergent strabismus on spatio-temporal response properties of neurons in cat area18
Exp. Brain Res.
Effects of rearing kittens with convergent strabismus on development of receptive-field properties in striate cortex neurons
J. Neurophysiol.
Receptive fields in the body-surface map in adult cortex defined by temporally correlated inputs
Nature
Eye-specific termination bands in tecta of three-eyed frogs
Science
Transient and prolonged facilitation of tone-evoked responses induced by basal forebrain stimulations in the rat auditory cortex
Exp. Brain Res.
Environmental enrichment improves response strength, threshold, selectivity, and latency of auditory cortex neurons
J. Neurophysiol.
Temporal integration in visual cortex of cats with surgically induced strabismus
Eur J. Neurosci.
Spike-timing-dependent synaptic modification induced by natural spike trains
Nature
The Organization of Behavior
Cited by (17)
Acetylcholine bidirectionally regulates learning and memory
2022, Journal of NeurorestoratologyDirecting neural plasticity to understand and treat tinnitus
2013, Hearing ResearchCitation Excerpt :We demonstrated that NB-tone pairing also resulted in dramatic map reorganization in the secondary auditory cortex (Puckett et al., 2007). By pairing more complex stimuli with NB stimulation, we can enhance neural sensitivity, temporal processing, and frequency selectivity of A1 neurons (Kilgard and Merzenich, 1998b, 2002; Kilgard et al., 2001, 2002; Pandya et al., 2005; Moucha et al., 2005). For example, pairing NB stimulation with tones of multiple frequencies greatly improved frequency selectivity of A1 neurons (Kilgard et al., 2001).
Harnessing plasticity to understand learning and treat disease
2012, Trends in NeurosciencesCitation Excerpt :The ideal method to test whether pathological plasticity is directly responsible for these sensations would be to reverse the plasticity and evaluate the perceptual consequence [9]. Studies in animals have shown that repeatedly pairing sensory stimuli with electrical stimulation of the cholinergic nucleus basalis (NB) of the basal forebrain generates precise, powerful, and long-lasting changes in cortical organization [10–19]. In principle, this method could be used to reverse the effect of pathological plasticity [20].
Attention effects on auditory scene analysis in children
2009, NeuropsychologiaLearning to hear: plasticity of auditory cortical processing
2007, Current Opinion in NeurobiologyCitation Excerpt :However, this seems not to be the case in the auditory cortex, as near complete elimination of cortical projections from the cholinergic basal forebrain does not affect the reorganization of the frequency map in A1 resulting from partial cochlear lesions [3•]. Whilst this result casts doubt on the exact role played by the cholinergic projection to the cortex in auditory representational plasticity, it has been shown in numerous studies that pairing electrical stimulation of the NB with sound presentation produces stimulus-specific changes in A1 response properties and map reorganization, which resemble the plasticity produced by classical conditioning or by long-term behavioural training [42–46]. Moreover, blockade of cortical acetylcholine receptors prevents the receptive field plasticity that would otherwise result from conditioning [47] or NB stimulation [48–50], while mice lacking the M1 muscarinic receptor subtype show weaker NB-stimulation-induced changes [51].
Chapter 7 Cortical plasticity and rehabilitation
2006, Progress in Brain ResearchCitation Excerpt :In the developing visual system, for example, alternating asynchronous electrical stimulation of the optic nerve prevents normal development of binocular visual responses (Stryker and Strickland, 1984). In auditory cortex, sounds designed to decrease or increase correlation across the frequency map lead to very different forms of plasticity (Pandya et al., 2005). Alternating activation of two nonoverlapping auditory neuron populations by two tones of distant frequencies (2 and 14 kHz) results in map segregation, decreased excitability, and longer response latencies of the activated neurons.