Heterosynaptic Facilitation of In Vivo Thalamocortical Long-Term Potentiation in the Adult Rat Visual Cortex by Acetylcholine

Abstract

Acetylcholine (ACh) plays a permissive role in developmental plasticity of fibers from the lateral geniculate nucleus (LGN) to the primary visual cortex (V1). These fibers remain plastic and express long-term potentiation (LTP) in adult rodents, but it is not known if ACh modulates this form of plasticity in the mature V1. We show that, in anesthetized rats, theta burst stimulation (TBS) of the LGN using 5 or 40 theta cycles produced moderate (approximately 20%) and stronger (approximately 40%) potentiation, respectively, of field postsynaptic potentials recorded in the ipsilateral V1. Basal forebrain stimulation (100 Hz) 5 min after TBS enhanced LTP induced by both weak (5 theta cycles) and strong (40 theta cycles) induction protocols. Both effects were reduced by systemic administration of the muscarinic receptor antagonist scopolamine. Basal forebrain stimulation did not enhance LTP when applied 30 min after or 5 min prior to TBS, suggesting that ACh affects early LTP induction mechanisms. Application of the cholinergic agonist carbachol in V1 by means of reverse microdialysis mimicked the effect of basal forebrain stimulation. We conclude that heterosynaptic facilitation of V1 plasticity by ACh extends beyond early postnatal maturation periods and acts to convert weak potentiation into pronounced, long-lasting increases in synaptic strength.

Training-induced plasticity in the visual cortex of adult rats following visual discrimination learning

“…Consistent with previous observations (Heynen and Bear 2001;Dringenberg et al 2007), single-pulse stimulation of the LGN elicited negative-going fPSPs recorded at the surface of the ipsilateral V1 (Fig. 4, insets).…”

“…TBS consisted of stimulation bursts (five pulses per burst at 100 Hz), with bursts repeated at 5 Hz for a total of 10 bursts (pulse duration and intensity same as above). These parameters were chosen based on previous work demonstrating robust, near-maximal LTP with this stimulation protocol (Dringenberg et al 2007). LFS consisted of 900 bursts (three pulses per burst at 20 Hz) repeated at 1 Hz, a protocol known to induce intermediate-term depression of V1 synapses in vivo (Hager and Dringenberg 2010).…”

Branch-Specific Plasticity Enables Self-Organization of Nonlinear Computation in Single Neurons

“…Some experimental data indicate that this form of plasticity needs dendritic spikes (Golding et al, 2002). Conversely, potentiation without dendritic spikes may be more pronounced in the presence of an increased concentration of ACh (Bröcher et al, 1992;Auerbach and Segal, 1994;Dringenberg et al, 2007). Also, a fairly large number of experimental data (Watt and Desai, 2010) support the existence of mechanisms for the so-called synaptic scaling, i.e., mechanisms that potentiate synapses of neurons whose average firing rate is very low, thereby bringing them back into a normal firing regimen.…”

“…Specifically, our model for branch-strength potentiation discussed below is based on findings of Losonczy et al (2008) for elevated cholinergic modulation levels. Furthermore, ACh can lower the threshold for LTP induction (Auerbach and Segal, 1994;Dringenberg et al, 2007). We thus assume that learning is enabled when local acetylcholine levels are elevated, which might signal exploratory behavior, saliency of the stimulus, or alertness.…”

“…Recent experimental data (Losonczy et al, 2008) also show that the coupling between dendritic branches and the soma (via dendritic spikes) is adapted through a mechanism called "branch-strength potentiation" (BSP), and evidence exists that BSP is relevant in vivo (Makara et al, 2009). Finally, synaptic and dendritic plasticity also depend on neuromodulatory input (Reynolds and Wickens, 2002;Gu, 2003;Dringenberg et al, 2007;Losonczy et al, 2008).…”