Neuromodulation and cortical function: modeling the physiological basis of behavior

Hasselmo, Michael E.

doi:10.1016/0166-4328(94)00113-t

Cited by 496 publications

(351 citation statements)

References 214 publications

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“…Neuromodulators generally have multiple effects in cortical circuits. For instance, they can change the DC firing rate of the neuron 37,38 ; this particular effect can be modelled as an additional depolarizing or hyperpolarizing current. Hence, in the model described above, neuromodulators can in principle alter the DC firing rate so that it approximately matches the oscillation frequency of the network that the neuron is embedded in.…”

Section: Stimulus Locking and Phase Lockingmentioning

confidence: 99%

Regulation of spike timing in visual cortical circuits

2008

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A train of action potentials (a spike train) can carry information in both the average firing rate and the pattern of spikes in the train. But can such a spike-pattern code be supported by cortical circuits? Neurons in vitro produce a spike pattern in response to the injection of a fluctuating current. However, cortical neurons in vivo are modulated by local oscillatory neuronal activity and by top-down inputs. In a cortical circuit, precise spike patterns thus reflect the interaction between internally generated activity and sensory information encoded by input spike trains. We review the evidence for precise and reliable spike timing in the cortex and discuss its computational role.Reliability and precision are two different quantities. When you make an appointment with your friend, she can either keep the appointment or not show up at all. If she does show up, she might or might not be on time. The former uncertainty is related to reliability, whereas the latter is related to precision. When the same stimulus waveform is repeatedly injected at the soma of a neuron in vitro (FIG. 1a), a similar spike train is obtained on each trial 1,2 (FIG. 1b). When approximately the same number of spikes occur on each trial the neuron is said to be reliable, whereas when the spikes occur almost at the same time across trials it is said to be precise (FIG. 1c). For a single neuron, the potential information content of precise and reliable spike times is many times larger than that which is contained in the firing rate, which is averaged across a typical interval of a hundred milliseconds [3][4][5][6] . The information contained in spike timing is available immediately, rather than after an averaging period. Furthermore, the timing of patterns of spikes can potentially transmit even more information than the timing of the individual constituent spikes 3,7 . The potential relevance of spike patterns becomes apparent when we consider neurons at the population level: when a group of similar neurons (a 'pool') produces precise and reliable spike trains, the neurons they project to receive volleys of synchronous spikes 8,9 . This opens up the possibility of communicating between different cortical areas through synchronous spike volleys.In contrast to the in vitro situation described above, in the intact cortex most excitatory synaptic inputs arrive at the dendrites rather than at the soma (FIG. 1d), and synaptic transmission is typically unreliable [10][11][12][13] . Furthermore, most of these dendritic inputs are not directly related to ongoing sensory stimulation; rather, they reflect spatiotemporally structured internal activity. Therefore, when the same stimulus is presented repeatedly, the resulting spike trains are usually neither precise nor reliable when they are aligned to the stimulus onset 6 . Instead, HHMI Author ManuscriptHHMI Author Manuscript HHMI Author Manuscript neural activity in vivo might be dominated by internally generated complex reverberations or rhythmic oscillations, and precise and reliable sp...

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Section: Stimulus Locking and Phase Lockingmentioning

confidence: 99%

Regulation of spike timing in visual cortical circuits

2008

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“…This causes a reduction of membrane K + conductance in cortical neurons, enhancing depolarization in response to glutamatergic input (McCormick and Prince, 1985) and reducing spike adaptation due to the after-hyperpolarization current (AHP, Hille, 2001) where τ r = 5ms and τ f = 6ms, and t is the time since the pre-synaptic cholinergic cell spikes (nucleus basalis of Maynert). These simulations investigate only the fast cholinergic dynamics, and do not address longer-lasting effect of ACh on target neural populations (Hasselmo, 1995). The cholinergic input acts by closing the normally open gate * g , therefore limiting the total AHP conductance when ACh modulation is active.…”

Section: Neurotransmitter Releasementioning

confidence: 99%

Spikes, synchrony, and attentive learning by laminar thalamocortical circuits

2008

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“…This allowed the model to automatically switch between two modes, a learning mode characterized by a high ACh release, and a retrieval mode characterized by a low ACh release. As ACh stimulates the formation of new patterns and also enhances LTP (Hasselmo, 1995;Hasselmo and Bower, 1993), such dynamics favor the formation of new representations in case of new input, and the maintenance of old representations in case of old input (Meeter et al, 2004). …”

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confidence: 99%

Effects of 5-HT on Memory and the Hippocampus: Model and Data

Meeter

Talamini

Schmitt

et al. 2005

Neuropsychopharmacol

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5-Hydroxytryptamine (5-HT) transmission has been implicated in memory and in depression. Both 5-HT depletion and specific 5-HT agonists lower memory performance, while depression is also associated with memory deficits. The precise neuropharmacology and neural mechanisms underlying these effects are unknown. We used neural network simulations to elucidate the neuropharmacology and network mechanisms underlying 5-HT effects on memory. The model predicts that these effects are largely dependent on transmission over the 5-HT 1A and 5-HT 3 receptors, which regulate the selectivity of retrieval. It also predicts differential memory deficit profiles for 5-HT depletion and overactivation. The latter predictions were confirmed in studies with healthy and depressed participants undergoing acute tryptophan depletion or ipsipirone challenge. The results suggest that the memory impairments in depressed subjects may be related to 5-HT undertransmission, and support the notion that 5-HT 1A agonists ameliorate memory deficits in depression. INTRODUCTIONHypofunction of the 5-hydroxytryptamine (5-HT) system has emerged as a leading candidate cause for depression (Naughton et al, 2000;Middlemiss et al, 2002). At the same time, several lines of evidence point to a role for 5-HT in memory (Buhot et al, 2000). Most prominently, depletion of tryptophan (TRP), a precursor of 5-HT, is associated with lower performance on episodic memory retention tests in humans (Riedel et al, 1999). This mirrors findings in depression, which is accompanied by moderate to severe memory deficits (Johnson and Magaro, 1987;Schaub et al, 2003). However, manipulations that increase 5-HT concentration or 5-HT receptor activation also lower memory performance, as indicated by receptor agonist studies in both humans (Riedel et al, 2002) and animals (Altman and Normile, 1988). Up to now, it is not known why both increased and decreased 5-HT activation have adverse effects on memory.5-HT binds to a large and disparate family of CNS receptors, which have effects that are sometimes opposite. Thus, many effects of different receptors seem to cancel each other out. In a review (see Supplementary Information on internet), we identify two robust effects of 5-HT in the hippocampus. First, 5-HT exerts a hyperpolarizing influence on principal cells; directly, via 5-HT 1A receptors, and indirectly, via facilitation of GABA release from local interneurons through 5-HT 3 receptors (Burnet et al, 1995;Piguet and Galvan, 1994). Activation of 5-HT 2A and 5-HT 2C receptors has been suggested to induce depolarization in principal cells (Piguet and Galvan, 1994;Barnes and Sharp, 1999), but these effects appear to be dominated by the depolarizing effects of 5-HT, as bath application of 5-HT will hyperpolarize principal cells in slice preparations of the dentate gyrus (Piguet and Galvan, 1994). In addition, through 5-HT 2C , 5-HT 4 , and 5-HT 7 receptors, afterhyperpolarizing (AHP) currents are downregulated, leading to reduced adaptation in principal cells (Torres et al, 1996;Bac...

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Neuromodulation and cortical function: modeling the physiological basis of behavior

Cited by 496 publications

References 214 publications

Regulation of spike timing in visual cortical circuits

Regulation of spike timing in visual cortical circuits

Spikes, synchrony, and attentive learning by laminar thalamocortical circuits

Effects of 5-HT on Memory and the Hippocampus: Model and Data

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