Biomedical subjects

Dean V Buonomano

Publications and source records attributed to Dean V Buonomano.

11 recordsLinked to original sources

PubMed2006

Different forms of homeostatic plasticity are engaged with distinct temporal profiles.

Global changes in network activity have been reported to induce homeostatic plasticity at multiple synaptic and cellular loci. Though individual types of plasticity are normally examined in isolation, it is their interactions and net effect that will ultimately determine their functional consequences. Here we examine homeostatic plasticity of both inhibition and intrinsic excitability in parallel in rat organotypic hippocampal slices. As previous studies have not examined inhibitory plasticity using a functional measure, inhibition was measured by the ability of evoked inhibitory postsynaptic potentials (IPSPs) to suppress action potentials, as well as IPSP amplitude. We show that manipulations of network activity can both up- and downregulate functional inhibition, as well as intrinsic excitability. However, these forms of plasticity are dissociable. Specifically, robust changes in intrinsic excitability were observed in the absence of inhibitory plasticity, and shifts in inhibition, but not excitability, appear to be sensitive to developmental stage. Our data establish that while the two forms of homeostatic plasticity can be engaged in parallel, there is a specific order in which they are expressed, with changes in excitability preceding those in inhibition. We propose that changes in intrinsic excitability occur first in order to stabilize network activity while optimizing the preservation of information stored in synaptic strengths by restricting changes that will disrupt the balance of synaptic excitation and inhibition.

2-Amino-5-phosphonovalerate↗

PubMed2005

A technique for repeated recordings in cortical organotypic slices.

Electrophysiology studies in vitro have generally focused on forms of plasticity which are rapidly induced and last for minutes to hours. However, it is well known that plasticity at some cellular and synaptic loci are induced and expressed over many hours or days. One limitation in examining these forms of plasticity is the lack of preparations that allow stimulation and recording of the same tissue over a 24h period or more. Here we describe a simple method for repeated recordings and stimulating the same organotypic slices (different neurons) over a 24h window. We use the conventional interface organotypic culture method together with a custom chamber, which allows recordings on the intact filter, and DiI to mark the stimulation sites. We show that the health of the neurons, as defined by intrinsic excitability, excitatory and inhibitory input-output curves, and morphology remains unchanged over the 24h period. This simple technique provides a means to investigate long-term forms of plasticity that may be induced under conditions similar to those observed in vivo. Additionally, it provides the opportunity to perform long-term morphological and pharmacological studies.

Action Potentials↗

PubMed2005

A learning rule for the emergence of stable dynamics and timing in recurrent networks.

Neural dynamics within recurrent cortical networks is an important component of neural processing. However, the learning rules that allow networks composed of hundreds or thousands of recurrently connected neurons to develop stable dynamical states are poorly understood. Here I use a neural network model to examine the emergence of stable dynamical states within recurrent networks. I describe a learning rule that can account both for the development of stable dynamics and guide networks to states that have been observed experimentally, specifically, states that instantiate a sparse code for time. Across trials, each neuron fires during a specific time window; by connecting the neurons to a hypothetical set of output units, it is possible to generate arbitrary spatial-temporal output patterns. Intertrial jitter of the spike time of a given neuron increases as a direct function of the delay at which it fires. These results establish a learning rule by which cortical networks can potentially process temporal information in a self-organizing manner, in the absence of specialized timing mechanisms.

Action Potentials↗

PubMed2004

Timing and balance of inhibition enhance the effect of long-term potentiation on cell firing.

The role of a neuron in neural processing is ultimately determined by whether or not it fires an action potential in a given context. Studies on synaptic plasticity have focused primarily on changes in EPSPs, and not on whether plasticity translates into changes in firing. However, this issue has been addressed by examining EPSP-spike (E-S) potentiation, which enhances the ability of an EPSP of a fixed slope to elicit spikes after long-term potentiation (LTP). Although LTP is thought to underlie learning and memory, E-S potentiation could play an equally important role by potentiating the neuronal input-output function. Here, we used a combined experimental and theoretical approach to examine both the mechanisms underlying E-S potentiation as well as the role of inhibition in shaping the input-output function of neurons. Whereas previous studies examined tetanus-LTP, in which inhibitory synapses may have undergone plasticity, here we examined pairing-induced associative LTP. We determined that although intact inhibition was necessary for pairing-induced E-S potentiation, inhibitory plasticity was not. We further established using computer simulations that a primary mechanism of E-S potentiation was a change in the relative recruitment and latency of inhibitory neurons. Although these studies do not exclude the presence of additional mechanisms of E-S potentiation that may be engaged depending on the induction protocol, they do establish that under intact pharmacology, LTP of the Schaffer collateral to CA1 pyramidal neuron synapses will produce E-S potentiation as a result of changes in the balance and timing of excitation and inhibition.

Action Potentials↗

PubMed2004

The neural basis of temporal processing.

A complete understanding of sensory and motor processing requires characterization of how the nervous system processes time in the range of tens to hundreds of milliseconds (ms). Temporal processing on this scale is required for simple sensory problems, such as interval, duration, and motion discrimination, as well as complex forms of sensory processing, such as speech recognition. Timing is also required for a wide range of motor tasks from eyelid conditioning to playing the piano. Here we review the behavioral, electrophysiological, and theoretical literature on the neural basis of temporal processing. These data suggest that temporal processing is likely to be distributed among different structures, rather than relying on a centralized timing area, as has been suggested in internal clock models. We also discuss whether temporal processing relies on specialized neural mechanisms, which perform temporal computations independent of spatial ones. We suggest that, given the intricate link between temporal and spatial information in most sensory and motor tasks, timing and spatial processing are intrinsic properties of neural function, and specialized timing mechanisms such as delay lines, oscillators, or a spectrum of different time constants are not required. Rather temporal processing may rely on state-dependent changes in network dynamics.

Animals↗

PubMed2003

Timing of neural responses in cortical organotypic slices.

Timing is a fundamental part of sensory and motor processing. However, little is known about the neural mechanisms underlying timing in the range of tens to hundreds of milliseconds. Although many theoretical hypotheses have been put forth on the possible underpinnings of temporal processing, there is little cellular experimental data, particularly in vitro, as to the neural mechanisms that could potentially function as timers. We use organotypic cortical slices to show that reliably timed action potentials (or excitatory postsynaptic potentials) can be observed up to 300 ms after a single stimulus. There was no relationship between the latency of the late responses and distance from the stimulating electrode. Paired recordings and pharmacological manipulations suggest that the timed late responses are the result of the propagation of activity throughout functionally defined networks. These results show that cortical networks may be intrinsically able to process temporal information.

2-Amino-5-phosphonovalerate↗

PubMed2003

Differential effects of short- and long-term potentiation on cell firing in the CA1 region of the hippocampus.

Long-term potentiation (LTP) in the hippocampus enhances the ability of a stimulus to produce cell firing, not only by increasing the strength of the EPSPs, but also by increasing the efficiency of the input/output (I/O) function of pyramidal neurons. This means that EPSPs of a given size more easily elicit spikes after LTP, a process known as EPSP-spike (E-S) potentiation. In contrast to LTP, it is not known whether the synaptic strengthening produced by paired-pulse facilitation (PPF) also results in changes in the I/O function. We have addressed this question by examining E-S curves from rat hippocampal area CA1 in response to both PPF and LTP. We describe a novel form of I/O modulation in which PPF produces E-S depression; that is, the E-S curve is shifted to the right, indicating a decreased ability of EPSPs to elicit action potentials. Consistent with the notion that E-S potentiation observed with LTP is caused by long-term increases in the excitatory-inhibitory ratio, we show that PPF-induced E-S depression relies on short-term decreases in this ratio. These results indicate that different forms of synaptic plasticity that produce the same degree of EPSP potentiation can result in dramatically different effects on cell firing, because of the dynamic changes in the excitatory-inhibitory balance within local circuits.

Action Potentials↗

PubMed2002

Mechanisms and significance of spike-timing dependent plasticity.

Hebb's original postulate left two important issues unaddressed: (i) what is the effective time window between pre- and postsynaptic activity that will result in potentiation? and (ii) what is the learning rule that underlies decreases in synaptic strength? While research over the past 2 decades has addressed these questions, several studies within the past 5 years have shown that synapses undergo long-term depression (LTD) or long-term potentiation (LTP) depending on the order of activity in the pre- and postsynaptic cells. This process has been referred to as spike-timing dependent plasticity (STDP). Here we discuss the experimental data on STDP, and develop models of the mechanisms that may underlie it. Specifically, we examine whether the standard model of LTP and LTD in which high and low levels of Ca(2+) produce LTP and LTD, respectively, can also account for STDP. We conclude that the standard model can account for a type of STDP in which, counterintuitively, LTD will be observed at some intervals in which the presynaptic cell fires before the postsynaptic cell. This form of STDP will also be sensitive to parameters such as the presence of an after depolarization following an action potential. Indeed, the sensitivity of this type of STDP to experimental parameters suggests that it may not play an important physiological role in vivo. We suggest that more robust forms of STDP, which do not exhibit LTD at pre-before-post intervals, are not accounted for by the standard model, and are likely to rely on a second coincidence detector in addition to the NMDA receptor.

Action Potentials↗

PubMed2002

A model of spike-timing dependent plasticity: one or two coincidence detectors?

In spike-timing dependent plasticity (STDP), synapses exhibit LTD or LTP depending on the order of activity in the presynaptic and postsynaptic cells. LTP occurs when a single presynaptic spike precedes a postsynaptic one (a positive interspike interval, or ISI), while the reverse order of activity (a negative ISI) produces LTD. A fundamental question is whether the "standard model" of plasticity in which moderate increases in Ca(2+) influx through the N-methyl-D-aspartate (NMDA) channels induce LTD and large increases induce LTP, can account for the order and interval sensitivity of STDP. To examine this issue we developed a model that captures postsynaptic Ca(2+) influx dynamics and the associativity of the NMDA receptors. While this model can generate both LTD and LTP, it predicts that LTD will be observed at both negative and positive ISIs. This is because longer and longer positive ISIs induce monotonically decreasing levels of Ca(2+), which eventually fall into the same range that produced LTD at negative ISIs. A second model that incorporated a second coincidence detector in addition to the NMDA receptor generated LTP at positive intervals and LTD only at negative ones. Our findings suggest that a single coincidence detector model based on the standard model of plasticity cannot account for order-specific STDP, and we predict that STDP requires two coincidence detectors.

Action Potentials↗

PubMed2002

How do we tell time?

Animals time events on scales that range more than 10 orders of magnitude-from microseconds to days. This review focuses on timing that occurs in the range of tens to hundreds of milliseconds. It is within this range that virtually all the temporal cues for speech discrimination, and haptic and visual processing, occur. Additionally, on the motor side, it is on this scale that timing of fine motor movements takes place. To date, psychophysical data indicate that for many tasks there is a centralized timing mechanism, but that there are separate networks for different intervals. These data are supported by experiments that show that training to discriminate between two intervals generalizes to different modalities, but not different intervals. The mechanistic underpinnings of timing are not known. However various models have been proposed, they can be divided into labeled-line models and population clocks. In labeled-line models, different intervals are coded by activity in independent and discrete populations of neurons. In population models, time is coded by the population activity of a large group of neurons, and timing requires dynamic interaction between neurons. Population models are generally better suited for parallel processing of interval, duration, order, and sequence cues and are thus more likely to underlie timing in the range of tens to hundreds of milliseconds.

Animals↗

PubMedDate not supplied

Temporal specificity of perceptual learning in an auditory discrimination task.

Although temporal processing is used in a wide range of sensory and motor tasks, there is little evidence as to whether a single centralized clock or a distributed system underlies timing in the range of tens to hundreds of milliseconds. We investigated this question by studying whether learning on an auditory interval discrimination task generalizes across stimulus types, intervals, and frequencies. The degree to which improvements in timing carry over to different stimulus features constrains the neural mechanisms underlying timing. Human subjects trained on a 100- or 200-msec interval discrimination task showed an improvement in temporal resolution. This learning generalized to a perceptually distinct duration stimulus, as well as to the trained interval presented with tones at untrained spectral frequencies. The improvement in performance did not generalize to untrained intervals. To determine if spectral generalization was dependent on the importance of frequency information in the task, subjects were simultaneously trained on two different intervals identified by frequency. As a whole, our results indicate that the brain uses circuits that are dedicated to specific time spans, and that each circuit processes stimuli across nontemporal stimulus features. The patterns of generalization additionally indicate that temporal learning does not rely on changes in early, subcortical processing, because the nontemporal features are encoded by different channels at early stages.

Adult↗