Motivationally neutral stimulation of the nucleus basalis induces specific behavioral memory

Abstract

The cholinergic system has been implicated in learning and memory. The nucleus basalis (NB) provides acetylcholine (ACh) to the cerebral cortex. Pairing a tone with NB stimulation (NBstm) to alter cortical state induces both associative specific tuning plasticity in the primary auditory cortex (A1) and associative specific auditory behavioral memory. NB-induced memory has major features of natural memory that is induced by pairing a tone with motivational reinforcers, e.g., food or shock, suggesting that the cholinergic system may be a "final common pathway" whose activation promotes memory storage. Alternatively, NB-stimulation might itself be motivationally significant, either rewarding or punishing. To investigate these alternatives, adult male rats (n = 7) first formed a specific NB-induced memory (CS = 8.0 kHz, 2.0 s paired with NBstm, ISI = 1.8 s, 200 trials), validated by post-training (24 h) frequency generalization gradients (1-15 kHz) of respiration interruption that were specific to the CS frequency. Thereafter, they received the same level of NBstm that had induced memory, while confined to one quadrant of an arena, and later tested for place preference, i.e., avoidance or seeking of the quadrant of NBstm. This NBstm group exhibited neither preference for nor against the stimulated quadrant, compared to sham-operated subjects (n = 7). The findings indicate that specific associative memory can be induced by direct activation of the NB without detectable motivational effects of NB stimulation. These results are concordant with a memorypromoting role for the nucleus basalis that places it "downstream" of motivational systems, which activate it to initiate the storage of the current state of its cholinergic targets.

Resting state functional connectivity of the basal nucleus of Meynert in humans: In comparison to the ventral striatum and the effects of age

“…Other work suggests that the BNM neurons encode saliency irrespective of valence of the stimuli (Lin and Nicolelis, 2008). These results are concordant with a learning-related or memory-promoting role for the BNM that places it “downstream” of motivational systems (Miasnikov et al, 2008), consistent with the anatomical finding that, the cholinergic neurons in basal forebrain receive input from the nucleus accumbens (Zaborszky and Cullinan, 1992). Through its extensive cortical projections, the BNM may mediate attentional effort in a circuitry that integrates brain systems involved in modulation of input functions, incentive processing and performance monitoring (Sarter et al, 2006).…”

“…In particular, the BNM may mediate learning and memory even when such processes are motivationally neutral. In behavioral conditioning of rats, specific associative memory can be induced by direct activation of the BNM without detectable motivational effects as in seeking reward or avoiding punishment (Miasnikov et al, 2008). Indeed, neurons in the BNM did not respond to primary reinforcers, positive (juice) or negative (salt water), in monkeys (Wilson and Rolls, 1990).…”

Cortical Synaptic Inhibition Declines during Auditory Learning

“…The learning-associated decrease in inhibitory gain is likely to involve cholinergic activity during training. When paired with sensory stimulation, stimulation of cholinergic nucleus basalis afferents to cortex induces long-lasting modifications to cortical response properties (Tremblay et al, 1990;Ashe, 1992, 1993;Edeline et al, 1994;Kilgard and Merzenich, 1998) and is sufficient for memory formation and improved sensory perception (Miasnikov et al, 2008;Bieszczad et al, 2013;Froemke et al, 2013). In the present study, the greatest change in inhibitory synaptic function occurred during procedural learning of the auditory task (Figs.…”

Gamma band plasticity in sensory cortex is a signature of the strongest memory rather than memory of the training stimulus

“…Implanted memory is not an artifact of putative local or spreading rewarding (Wilson & Rolls, 1990) or punishing stimulation because it is induced by low currents, producing brief EEG activation without overt behavioral change and the level of current controls the specificity of memory rather than the strength of learning (Weinberger et al, 2006). Also, NBstm inducing memory is motivationally neutral (Miasnikov et al, 2008a) and implanted memory is dependent on central muscarinic receptors (Miasnikov et al, 2008b). Therefore, the cholinergic system may play a pivotal enabling role in the formation of cortically-based associative memory.…”

“…The effect of pairing the CS with NBstm on memory was determined by subtracting the pre-training FGG on Day 2 from the post-training FGG on Day 6, yielding a difference frequency generalization gradient (ΔFGG) (see Section 2.4). A non-associative control group was not included because all previous studies of NB-induced memory implantation have shown that the effects of pairing tone with NBstm (tone–NBstm) are associative (McLin, Miasnikov, & Weinberger, 2002a; Miasnikov, Chen, Gross, Poytress, & Weinberger, 2008a; Miasnikov, Chen, & Weinberger, 2006, 2008b, 2011; Weinberger et al, 2006). …”