Abstract
The neurotransmitter dopamine (DA) plays an important role in learning by enhancing the saliency of behaviorally relevant stimuli. How this stimulus selection is achieved on the cellular level, however, is not known. Here, in recordings from hippocampal slices, we show that DA acts specifically at the direct cortical input to hippocampal area CA1 (the temporoammonic (TA) pathway) to filter the excitatory drive onto pyramidal neurons based on the input frequency. During low-frequency patterns of stimulation, DA depressed excitatory TA inputs to both CA1 pyramidal neurons and local inhibitory GABAergic interneurons via presynaptic inhibition. In contrast, during high-frequency patterns of stimulation, DA potently facilitated the TA excitatory drive onto CA1 pyramidal neurons, owing to diminished feedforward inhibition. Analysis of DA's effects over a broad range of stimulus frequencies indicates that it acts as a high-pass filter, augmenting the response to high-frequency inputs while diminishing the impact of low-frequency inputs. These modulatory effects of DA exert a profound influence on activity-dependent forms of synaptic plasticity at both TA-CA1 and Schaffer-collateral (SC)-CA1 synapses. Taken together, our data demonstrate that DA acts as a gate on the direct cortical input to the hippocampus, modulating information flow and synaptic plasticity in a frequency-dependent manner.
Highlights
Midbrain dopaminergic neurons increase their firing activity when animals receive unexpected rewards or experience a novel environment––both the hedonic value and familiarity of stimuli are important determinants in learning (Horvitz, 2000; Schultz and Dickinson, 2000)
DA selectively depresses excitatory synaptic transmission at TA-CA1 pyramidal neuron synapses To examine the differential influence of DA on the two excitatory inputs to area CA1, we made extracellular field recordings from both the SC pathway and the TA pathway in hippocampal slices (Figure 1A)
How quickly can the network adapt to DA signals? Because dopaminergic neurons show both tonic and burst-like activity patterns in vivo (Floresco et al, 2003; Grace, 1991), we examined the sensitivity of this modulation to very brief (10 second + 1–2 minute washout) temporally controlled applications of DA (Figures 8A and 8B)
Summary
Midbrain dopaminergic neurons increase their firing activity when animals receive unexpected rewards or experience a novel environment––both the hedonic value and familiarity of stimuli are important determinants in learning (Horvitz, 2000; Schultz and Dickinson, 2000). One of the targets of dopaminergic neurons is the hippocampus, a brain structure crucial for some types of learning and memory (Gasbarri et al, 1994a, 1994b, 1996a; Scoville and Milner, 1957; Squire et al, 2004; Swanson, 1982; Zola-Morgan and Squire, 1986). The primary targets of dopaminergic neurons are the subiculum and area CA1 (Gasbarri et al, 1997). Each pathway appears to have a distinct function in learning (Brun et al, 2002; Remondes and Schuman, 2004; Steffenach et al, 2002) and may be differentially
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