Neuromodulation of neuronal circuits: back to the future - PubMed (original) (raw)

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Neuromodulation of neuronal circuits: back to the future

Eve Marder. Neuron. 2012.

Abstract

All nervous systems are subject to neuromodulation. Neuromodulators can be delivered as local hormones, as cotransmitters in projection neurons, and through the general circulation. Because neuromodulators can transform the intrinsic firing properties of circuit neurons and alter effective synaptic strength, neuromodulatory substances reconfigure neuronal circuits, often massively altering their output. Thus, the anatomical connectome provides a minimal structure and the neuromodulatory environment constructs and specifies the functional circuits that give rise to behavior.

Copyright © 2012 Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1

Intrinsic and Extrinsic Modulation. Extrinsic modulation comes from outside the circuit or modulated target. Intrinsic modulation refers to neurons that are part of a circuit and release modulators that can alter the properties of other circuit elements. Drawing loosely after Katz and Frost (Katz and Frost, 1996).

Figure 2

Figure 2

Partial Summary of Neuromodulation of the crab stomatogastric ganglion (STG). The STG sits anterior to the heart within an artery that brings modulatory amines and peptides from neurosecretory structures such as the pericardial organs (bottom list). 25 pairs of descending modulatory neurons bring a host of substances into the neuropil of the STG (right). The number of family members of the neuropeptides are shown in parentheses. Figure was made by D. Bucher, summarizing work from the Li and Stemmler labs and numerous collaborators.

Figure 3

Figure 3

Multiple neuromodulators can activate different forms of the pyloric rhythm. In each panel the top two traces are intracellular recordings from the Lateral Pyloric (LP) and Pyloric Dilator (PD) neurons. The bottom trace is an extracellular recording from the lateral ventricular nerve (lvn) that carries the axons of the LP, PD, and Pyloric (PY) neurons. (Marder and Weimann, 1992).

Figure 4

Figure 4

Modulatory reconfiguration of circuits. A) Three different proctolin-containing modulatory neurons each evoke different changes in STG motor patterns. (Blitz et al., 1999; Nusbaum et al., 2001). B) Bath application of RPCH constructs a conjoint rhythm from previously separate cardiac sac and gastric mill circuit elements. Modified from Dickinson et al (1990).

Figure 5

Figure 5

Aminergic modulation of pyloric circuit elements. A) The actions of dopamine on ionic currents in the indicated neurons are shown. From (Harris-Warrick, 2011). B) Graded IPSPs evoked in the postsynaptic PD neuron by depolarization of the LP neuron in control (black traces), dopamine (red), octopamine (blue) and serotonin (green). Modified from Johnston et al (2011).

Figure 6

Figure 6

Effects of modulatory substances on a bursting pacemaker neuron, A) Intracellular recordings from the isolated Anterior Burster (AB) neuron in control and proctolin. Modified from Hooper and Marder (1987). Notice the increase in amplitude without change in baseline. B) AB neuron in response to nicotine and pilocarpine.

Figure 7

Figure 7

Multiple modulators act on the same neuron and converge onto the same current. A) Puff applications of the modulators indicated onto intracellularly recorded LP neuron. (Swensen and Marder, 2000). B) Voltage-clamp recordings of inward currents evoked by proctolin and CabTRP1a. Top traces, puff of proctolin elicited an inward current. When CabTRP1a was placed in the bath, eliciting a steady-state inward current, a puff of proctolin produced only a very small additional inward current. Bottom traces, reverse experiment. (Swensen and Marder, 2000).

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