Temporal overlap of excitatory and inhibitory afferent input in guinea‐pig CA1 pyramidal cells

Abstract

The response to afferent fibre stimulation ('orthodromic response') is a commonly used measure of excitability of neuronal populations. An excitatory (EPSP) and inhibitory (IPSP) component was identified by studies of the orthodromic response in hippocampal pyramidal cells in vivo (Kandel et al. 1961;Andersen et al. 1963Andersen et al. , 1964. This basic sequence of orthodromic EPSP-IPSP has been confirmed since then: the response that is elicited by stimulation of the Schaffer collateral-commissural pathway consists of a fast EPSPÏEPSC mediated primarily by AMPA receptors, followed by an early IPSPÏIPSC mediated by GABAA receptors and a late IPSPÏIPSC mediated by GABAB receptors. Despite such clear separation of postsynaptic potentials (PSPs) or currents (PSCs), it is conceivable that inhibitory influences may be present long before the population IPSP is expressed. If so, how large is the temporal overlap with the orthodromic EPSPÏEPSC?This study has focused on three points. First, the kinetics of dendritic inhibition were studied. Several previous studies have reported that the kinetics of dendritic inhibitory responses were slower than those of somatic responses in pyramidal cells (Miles, 1990b;Pearce, 1993;Buhl et al. 1994a). Second, kinetics of different inhibitory responses, i.e. IPSPs, IPSCs and conductance changes, were investigated. It was suggested that inhibitory conductance changes are faster than IPSPs (Araki et al. 1960) or inhibitory currents (Koch, 1985). Third, time courses of various components of the circuitry were studied: a monosynaptic inhibitory response is elicited via direct electrical stimulation of interneuron processes (Davies et al. 1990). Activation of afferent fibres results in a feedforward inhibitory response in CA1 pyramidal cells via synaptic activation of CA1 interneurons (Knowles & Schwartzkroin, 1981;Alger & Nicoll, 1982;Buzsaki & Eidelberg, 1982; Ashwood et al. Journal of Physiology (1999) but > 3·0 ms after the peak of the pyramidal cell EPSP. 6. Orthodromically evoked interneuron spikes were observed at stimulation intensities that were below the threshold for eliciting EPSPs in concomitantly recorded pyramidal cells. The activation of feedforward inhibitory responses by weakest excitatory input, and the large temporal overlap between feedforward inhibition and evoked excitation, suggest that in situ any excitatory input in CA1 is effectively controlled by fast synaptic inhibition. Keywords:

Timing and Balance of Inhibition Enhance the Effect of Long-Term Potentiation on Cell Firing

“…By comparing A and C in Figure 7, it appears that shifts in E 50 did not occur in the conditions corresponding to either the floor or saturation states of the inhibitory neurons. We argue that the range of states in which E-S potentiation occurred is precisely the physiological range, because inhibition and excitation are normally recruited in a balanced manner that allows inhibition to have an impact on Ex neuron activity (Galarreta and Hestrin, 1998;Karnup and Stelzer, 1999;Pouille and Scanziani, 2001). Moreover, inhibitory neurons are driven by fewer input fibers than excitatory neurons (Miles, 1990;Marshall et al, 2002), consistent with the data shown in the middle and bottom panels of Figure 6C.…”

“…If all intensities of the Ex neuron I/O curves before and after LTP elicited similar inhibition, then the same EPSP slope led to the same firing probability, and E-S shifts did not occur. Previous results suggest that the physiological state is indeed one in which excitation is balanced with inhibition (Galarreta and Hestrin, 1998;Karnup and Stelzer, 1999;Pouille and Scanziani, 2001). Therefore, our data indicate that a primary mechanism of E-S potentiation is that EPSPs of a fixed slope evoked after LTP have less effective inhibition and thus a greater probability of reaching firing threshold.…”

“…The total synaptic weight onto each Inh neuron was varied so that increases in intensity corresponded to increases in the number of Inh neurons recruited. The synaptic delays and cellular parameters (see below) were chosen to reflect published electrophysiological data on excitatory and inhibitory cells in the hippocampus (Brown et al, 1981;Lacaille et al, 1987;Spruston and Johnston, 1992;Karnup and Stelzer, 1999). Inh units exhibited a lower threshold and faster time constant than Ex units, so that Inh units were easier to drive than Ex units, consistent with evidence that single-action potentials in pyramidal neurons can trigger spikes in inhibitory neurons (Miles, 1990;Marshall et al, 2002).…”

“…lished that the timing of the arrival of excitation and inhibition plays a powerful role in controlling Ex neuron firing (Karnup and Stelzer, 1999;Fricker and Miles, 2000;Pouille and Scanziani, 2001) (see Discussion). The increase in the latency of Inh neurons observed here was critical for E-S potentiation because it allowed the Ex neuron to reach a greater peak depolarization before the onset of a significant degree of inhibition.…”

Olfactory Bulb External Tufted Cells Are Synchronized by Multiple Intraglomerular Mechanisms

“…Tetrodotoxin (TTX), QX-314, gabazine [SR95531 (2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide)], 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and (Ϯ)-2-amino-5-phosphopentanoic acid (APV) were purchased from Research Biochemicals (Natick, MA). Biocytin-filled cells were developed as described previously (Karnup and Stelzer, 1999). Briefly, fixed slices were embedded in 10% gelatin and sectioned at 80 m thickness using a vibratome.…”