Synaptic Bombardment Modulates Muscarinic Effects in Forelimb Motor Cortex

Niraj S. Desai and Elisabeth C. Walcott

Continuous synaptic bombardment with a complex barrage of excitatory and inhibitory inputs alter many aspects of neuronal responsiveness (by depolarizing neurons, increasing membrane conductance, and introducing fluctuations). This study shows how it shapes neuromodulation of postsynaptic responses by examining muscarinic modulation of forelimb motor cortex, a brain area in which cholinergic stimulation is known to be necessary for modifications during motor skill learning. Using a dynamic clamp system to inject simulated conductances
into pyramidal neurons, they mimicked in vivo-like activity by introducing a random background of excitatory and
inhibitory inputs. The presence of such background conductances strongly attenuated most muscarinic neuromodulatory effects, with the notable exception that sustained firing responses to trains of inputs were well preserved. This may be important for promoting plasticity in vivo.

The Journal of Neuroscience, February 22, 2006 • 26(8):2215–2226


Similar thing may be happening in the slug's CPG in the sea water. Most of my experiments testing neuromodulation have been done in HiDi saline, which suppresses anonymous synaptic bombardment.

Neurotrophins mediates a rapid switch in transmitter release

Bo Yang, John D. Slonimsky and Susan J. Birren

Brain-derived neurotrophic factor (BDNF) altered the neurotrasmitter release properties of sympathetic neuron-myocyte connections in rodent cell culture, leading to a rapid shift from excitatory norepinephrinic transmission to inhibitory cholinergic trasmission.

p75 neurotophin receptor mediates modulation of release of distinct neurotransmitter pools, resulting functinoal switch between excitatory and inhibitory neurotoransmission in individual neurons.

Nature Neuroscience 5(6) 539-545 (2002).

From IPSPs to EPSPs: Transition to seizures in the mouse hippocampus

Transition to seizures in the isolated immature mouse hippocampus: a switch from dominant phasic inhibition to dominant phasic excitation.
M. Derchansky, S. S. Jahromi, M. Manami, D.S. Shin, A. Sik, and P. L. Carlen

Neuronal networks can display non-linear complex behaviours that result in multiple stable states, with the capacity to undergo spontaneous transition between these states. An in vitro model of temporal lobe epilepsy (TLE) generates recurrent seizure-like events. The authors studied the sequence of inhibitory and excitatory events during the preictal state.

In animal models of epilepsy, dendritic but not somatic GABAergic inhibition is decreased and it has been hypothesized that this is the mechanism responsible for ictal generation.
Anothor hypothesis for ictal generation is that interneurons might be involved in synchronizing large neuronal populatios. This synchronization is possible by their abundant connectivity to pyramidal cells. Excitation might be achieved by the alteration of the intracellular chloride gradient after prolonged high-frequency activation of GABA-A receptor.


During the preictal state, there was a total reversal in the polarity of the synaptic potentials in pyramidal cells, fast-spiking cells, and non-FS cells.

The hyperpolarizing potentials during preictal state are generated by recurrent IPSPs (Cl-).
However, the reversal is not due to the change in the reversal potential for Cl ion. The authors suggest that the excitatory drive was produced by a complex change in the synaptic interactions among pyramidal cells and interneurons.

J. Physiol. 586.2, 477-494 (2008).