Ventral tegmental area disruption selectively affects CA1/CA2 but not CA3 place fields during a differential reward working memory task

Abstract

Hippocampus (HPC) receives dopaminergic (DA) projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences HPC dependent behaviors and place fields. We examined how efferent projections from VTA to HPC influence spatial working memory and place fields when the reward context changes. CA1 and CA3 process environmental context changes differently and VTA preferentially innervates CA1. Given these anatomical data and electrophysiological evidence that implicates DA in reward processing, we predicted that CA1 place fields would respond more strongly to both VTA disruption and changes in the reward context than CA3 place fields.Rats (N=9) were implanted with infusion cannula targeting VTA and recording tetrodes aimed at HPC. Then they were tested on a differential reward, win-shift working memory task. One recording session consisted of 5 baseline and 5 manipulation trials during which place cells in CA1/CA2 (N=167) and CA3 (N=94) were recorded. Prior to manipulation trials rats were infused with either baclofen or saline and then subjected to control or reward conditions during which the learned locations of large and small reward quantities were reversed. VTA disruption resulted in an increase in errors, and in CA1/CA2 place field reorganization. There were no changes in any measures of CA3 place field stability during VTA disruption. Reward manipulations did not affect performance or place field stability in CA1/CA2 or CA3; however, changes in the reward locations "rescued" performance and place field stability in CA1/CA2 when VTA activity was compromised, perhaps by trigging compensatory mechanisms. These data support the hypothesis that VTA contributes to spatial working memory performance perhaps specifically by maintaining place field stability selectively in CA1/CA2.

Rediscovering area CA2: unique properties and functions

“…3). Mankin et al 85 found that CA2 neurons, similar to those in the other CA fields, display place fields, consistent with a previous study that reported little difference in spatial firing between CA1 and CA2 neurons in rats exploring a radial arm maze 86 . However, CA2 place fields were later found to be slightly greater in number and larger in size than those in the CA1 and CA3 (REF.…”

Ventral tegmental area and substantia nigra neural correlates of spatial learning

“…VTA input to HPC may be direct (Gasbarri et al 1994), whereas HPC output to VTA is likely indirect, arriving via an accumbens to ventral pallidal to pedunculopontine nucleus route (Yang and Mogenson 1987;Floresco et al 2001). Supporting this view, VTA has been shown to regulate HPC neural activity during spatial learning (Martig and Mizumori 2011) and encoding of HPC-dependent memories (Rossato et al 2009). The pedunculopontine nucleus has been shown to regulate DA neuron firing (Kelland et al 1993;Floresco et al 2003;Zweifel et al 2009) and HPC regulates VTA DA neuron firing (Floresco et al 2001).…”

“…Intrahippocampal injections of DA agonists and antagonists improve and impair HPC-dependent behaviors, respectively (Packard and White 1991;Gasbarri et al 1996;Bernabeu et al 1997;O'Carroll et al 2006;Bethus et al 2010). The majority of DA innervations to HPC arise from the VTA (Gasbarri et al 1994), and VTA inactivation disrupts HPC-dependent learning, memory, and place fields Rossato et al 2009;Martig and Mizumori 2011). …”

A role for the lateral dorsal tegmentum in memory and decision neural circuitry

“…Martig et al, 2011a; Norton et al, 2011; Puryear et al, 2010). Each tetrode was made of four 25μm tungsten wires that were gold plated to achieve impedances of 100 to 400 kΩ.…”

“…However, LDTg lesions result in the attenuation of drug-induced stereotypy and sensitization (Forster et al, 2002; Laviolette et al, 2000; Nelson et al, 2007), effects likely mediated via mesencephalic and medullary efferents that control patterned limb movements (Brudzynski et al, 1988; Mogenson et al, 1980). Here, we test the nature of LDTg neural codes in a task that a) has a strong and directed locomotion component, b) has a specific reward-based econometric demands, c) induces VTA and PPTg neural responses to reward value (Jo et al, 2013; Martig et al, 2011b; Norton et al, 2011; Puryear et al, 2010), and d) requires VTA functionality (Martig et al, 2009, 2011a). In Experiment 1, the LDTg was inactivated while rats performed a spatial-reward discrimination task.…”